automated-radiochemical-synthesis-18f3f4ap-novel-pet-tracer-for

Automated Radiochemical Synthesis of [<sup>18</sup>F]3F4AP: A Novel PET Tracer for Imaging Demyelinating Diseases

3-[18F]fluoro-4-aminopyridine, [18F]3F4AP, is a radiofluorinated analog of the FDA-approved drug for multiple sclerosis 4-aminopyridine (4AP). This ...

The University of Chicago

A series of chlamydocin analogs with various carbonyl functionalities were designed and synthesized as histone deacetylase (HDAC) inhibitors. Chlamydocin is a cyclic tetrapeptide containing an epoxyketone surrogate in the side chain which makes it irreversible inhibitor of HDACs, whereas apicidins are a class of cyclic tetrapeptides that contain an ethylketone moiety as zinc ligand. We replaced the epoxyketone moiety of chlamydocin with several ketones and aldehyde to synthesize potent reversible and selective HDAC inhibitors. The inhibitory activity of the cyclic tetrapeptides against histone deacetylase enzymes were evaluated and the result showed most of them are potent inhibitors. Some of them have remarkable selectivity among the HDACs.

Chlamydocin analogs bearing carbonyl group as possible ligand toward zinc atom in histone deacetylases.

Inhibitors of histone deacetylases (HDACs) are a promising class of anticancer agents that effect gene regulation. To know the interaction of aliphatic cap groups with HDACs, cyclic tetrapeptide and bicyclic peptide disulfide hybrids were synthesized without aromatic ring in their macrocyclic framework. Benzene ring of l-Phe in chlamydocin was replaced with several aliphatic amino acids and also a fused bicyclic tetrapeptide was synthesized by ring closing metathesis using Grubb's first generation catalyst. The inhibitory activities of the cyclic peptides against histone deacetylase enzymes were evaluated, which demonstrated most of them are interesting candidates as anticancer agents.

Interaction of aliphatic cap group in inhibition of histone deacetylases by cyclic tetrapeptides.

Although irritable bowel syndrome (IBS) is a common gastrointestinal disorder, its prevalence is unknown, especially in the urban population of Bangladesh. This community-based study aimed to find out the prevalence of IBS and healthcare-seeking patterns using the Rome-II definition.

Irritable bowel syndrome in a Bangladeshi urban community: prevalence and health care seeking pattern.

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Chronic pressure ulcers affect patient health, emotional state, and quality of life, causing considerable morbidity and mortality in addition to contributing to significant health care costs from lengthy hospitalizations to advanced home care and surgical care costs. The conventional treatment of these wounds can be slow due to their chronic inflammatory state and the senescence of local reparative cells. Platelet-rich plasma (PRP) therapy has been growing as a viable treatment alternative for a number of clinical applications and has potential benefit for use in chronic wounds. The sustained release of large quantities of autologous growth factors, cytokines, and other mediators found in PRP plus the favorable mononuclear cell profile of PRP may help us to stimulate wound healing and resolve chronic inflammation.

A case report on the use of sustained release platelet-rich plasma for the treatment of chronic pressure ulcers.

Escarres chroniques affectent la sant&eacute; des patients, l&#39;&eacute;tat &eacute;motionnel et qualit&eacute; de vie, entra&icirc;nant une morbidit&eacute; et mortalit&eacute; en plus de contribuer aux co&ucirc;ts de sant&eacute; importants de longues hospitalisations pour des soins &agrave; domicile et les co&ucirc;ts des soins chirurgicaux. Le traitement conventionnel de ces blessures peut &ecirc;tre lent en raison de leur &eacute;tat inflammatoire chronique et la s&eacute;nescence des cellules r&eacute;paratrices locales. Th&eacute;rapie de plasma riche en plaquettes (PRP) a connu une croissance viable en traitement alternative pour un certain nombre d&#39;applications cliniques et a l&#39;avantage potentiel pour une utilisation dans les plaies chroniques. La lib&eacute;ration de grandes quantit&eacute;s de facteurs de croissance autologues, cytokines et d&#39;autres m&eacute;diateurs dans PRP plus le profil favorable de cellules mononucl&eacute;&eacute;es de PRP peut nous aider &agrave; stimuler la cicatrisation des plaies et r&eacute;soudre une inflammation chronique.

Un rapport de cas sur l&#39;utilisation de plasma riche en plaquettes &agrave; lib&eacute;ration prolong&eacute;e pour le traitement des ulc&egrave;res de pression chronique.

Chronischen Dekubitus beeinflussen die Gesundheit der Patienten, emotionalen Zustand und Lebensqualit&auml;t, verursachen erheblichen Morbidit&auml;t und Mortalit&auml;t zus&auml;tzlich zu erheblichen Kosten im Gesundheitswesen von l&auml;ngeren Hospitalisierungen erweiterte h&auml;usliche Pflege und die Kosten f&uuml;r chirurgische beitragen. Die konventionelle Behandlung dieser Wunden kann aufgrund ihrer chronischen entz&uuml;ndlichen Zustand und die Alterung des lokalen reparative Zellen langsam sein. Platelet-Rich Plasma (PRP) Therapie w&auml;chst als praktikable Behandlung alternative f&uuml;r eine Reihe von klinischen Anwendungen und potenziellen Nutzen f&uuml;r den Einsatz bei chronischen Wunden hat. Die nachhaltige Freisetzung gro&szlig;er Mengen von autologen Wachstumsfaktoren, Zytokine und anderer Vermittler gefunden in PRP sowie das g&uuml;nstige mononukle&auml;ren Zellen-Profil der PRP k&ouml;nnte uns zu stimulieren, Wundheilung und chronischen Entz&uuml;ndung beheben helfen.

Ein Fallbericht &uuml;ber die Verwendung von nachhaltigen Version Platelet-Rich Plasma f&uuml;r die Behandlung von chronischen Dekubitus.

Ulcere da pressione croniche possono influenzare la salute del paziente, lo stato emotivo e qualit&agrave; della vita, causando considerevole morbilit&agrave; e mortalit&agrave;, oltre a contribuire ai costi sanitari significativi da lunghe ospedalizzazioni per assistenza domiciliare avanzata e costi di cura chirurgica. Il trattamento convenzionale di queste ferite pu&ograve; essere lento a causa del loro stato infiammatorio cronico e la senescenza delle cellule riparative locali. La terapia di plasma ricco di piastrine (PRP) &egrave; in crescita come una valida terapia alternativa per un certo numero di applicazioni cliniche e ha il potenziale beneficio per l&#39;uso in ferite croniche. Il rilascio prolungato di grandi quantit&agrave; di fattori di crescita autologhi, citochine e altri mediatori trovati nel PRP pi&ugrave; il profilo favorevole delle cellule mononucleate del PRP possa aiutarci a stimolare la guarigione delle ferite e risolvere l&#39;infiammazione cronica.

Un rapporto di caso sull&#39;uso del plasma ricco di piastrine rilascio prolungato per il trattamento delle ulcere da pressione croniche.

&#x6162;&#x6027;&#x306E;&#x8925;&#x7621;&#x60A3;&#x8005;&#x306E;&#x5065;&#x5EB7;&#x3001;&#x611F;&#x60C5;&#x7684;&#x306A;&#x72B6;&#x614B;&#x3001;&#x304A;&#x3088;&#x3073;&#x304B;&#x306A;&#x308A;&#x306E;&#x7F79;&#x60A3;&#x7387;&#x3068;&#x6B7B;&#x4EA1;&#x7387;&#x306B;&#x52A0;&#x3048;&#x3066;&#x3001;&#x9577;&#x3044;&#x5165;&#x9662;&#x9AD8;&#x5EA6;&#x5728;&#x5B85;&#x4ECB;&#x8B77;&#x3001;&#x624B;&#x8853;&#x306E;&#x533B;&#x7642;&#x8CBB;&#x304B;&#x3089;&#x91CD;&#x8981;&#x306A;&#x533B;&#x7642;&#x8CBB;&#x306B;&#x8CA2;&#x732E;&#x306E;&#x539F;&#x56E0;&#x3068;&#x751F;&#x6D3B;&#x306E;&#x8CEA;&#x306B;&#x5F71;&#x97FF;&#x3092;&#x4E0E;&#x3048;&#x307E;&#x3059;&#x3002;&#x3053;&#x308C;&#x3089;&#x306E;&#x50B7;&#x306E;&#x5F93;&#x6765;&#x306E;&#x6CBB;&#x7642;&#x6CD5;&#x306F;&#x3001;&#x6162;&#x6027;&#x306E;&#x708E;&#x75C7;&#x72B6;&#x614B;&#x3068;&#x30ED;&#x30FC;&#x30AB;&#x30EB;&#x4FEE;&#x5FA9;&#x7D30;&#x80DE;&#x306E;&#x8001;&#x5316;&#x306E;&#x305F;&#x3081;&#x306B;&#x9045;&#x3044;&#x3053;&#x3068;&#x304C;&#x3067;&#x304D;&#x307E;&#x3059;&#x3002;&#x591A;&#x8840;&#x5C0F;&#x677F;&#x8840;&#x6F3F; (PRP) &#x7642;&#x6CD5;&#x306F;&#x5B9F;&#x884C;&#x53EF;&#x80FD;&#x306A;&#x6CBB;&#x7642;&#x3068;&#x3057;&#x3066;&#x81E8;&#x5E8A;&#x5FDC;&#x7528;&#x306E;&#x6570;&#x306E;&#x305F;&#x3081;&#x306B;&#x4EE3;&#x66FF;&#x6210;&#x9577;&#x3057;&#x3066;&#x3044;&#x308B;&#x3057;&#x3001;&#x50B7;&#x306E;&#x6162;&#x6027;&#x4F7F;&#x7528;&#x306E;&#x6F5C;&#x5728;&#x7684;&#x306A;&#x5229;&#x76CA;&#x3092;&#x3057;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x81EA;&#x5DF1;&#x6210;&#x9577;&#x56E0;&#x5B50;&#x3001;&#x30B5;&#x30A4;&#x30C8;&#x30AB;&#x30A4;&#x30F3;&#x3001;&#x304A;&#x3088;&#x3073; PRP + PRP &#x306E;&#x6709;&#x5229;&#x306A;&#x5358;&#x6838;&#x7D30;&#x80DE;&#x30D7;&#x30ED;&#x30D5;&#x30A1;&#x30A4;&#x30EB;&#x3067;&#x898B;&#x3064;&#x304B;&#x3063;&#x305F;&#x4ED6;&#x306E;&#x30E1;&#x30C7;&#x30A3;&#x30A8;&#x30FC;&#x30BF;&#x30FC;&#x306E;&#x5927;&#x91CF;&#x306E;&#x6301;&#x7D9A;&#x7684;&#x306A;&#x30EA;&#x30EA;&#x30FC;&#x30B9;&#x79C1;&#x305F;&#x3061;&#x5275;&#x50B7;&#x6CBB;&#x7652;&#x3092;&#x523A;&#x6FC0;&#x3057;&#x3001;&#x6162;&#x6027;&#x7684;&#x306A;&#x708E;&#x75C7;&#x3092;&#x89E3;&#x6C7A;&#x3059;&#x308B;&#x306E;&#x306B;&#x5F79;&#x7ACB;&#x3064;&#x3053;&#x3068;&#x304C;&#x3042;&#x308A;&#x307E;&#x3059;&#x3002;

&#x6162;&#x6027;&#x306E;&#x5727;&#x529B;&#x6F70;&#x760D;&#x6CBB;&#x7642;&#x306E;&#x305F;&#x3081;&#x306E;&#x5F90;&#x653E;&#x6027;&#x591A;&#x8840;&#x5C0F;&#x677F;&#x8840;&#x6F3F;&#x306E;&#x4F7F;&#x7528;&#x75C7;&#x4F8B;&#x5831;&#x544A;&#x3002;

&Uacute;lceras cr&oacute;nicas afectan la salud del paciente, estado emocional y calidad de vida, causando considerables morbosidad y mortalidad adem&aacute;s de contribuir a los costos de salud significativos de hospitalizaciones largas avanzado cuidado del hogar y los costos de la atenci&oacute;n quir&uacute;rgica. El tratamiento convencional de estas heridas puede ser lento debido a su estado inflamatorio cr&oacute;nico y la senescencia de c&eacute;lulas locales reparadores. Terapia de plasma rico en plaquetas (PRP) ha ido creciendo como un tratamiento viable alternativa para un n&uacute;mero de aplicaciones cl&iacute;nicas y tiene un beneficio potencial para el uso en heridas cr&oacute;nicas. La liberaci&oacute;n de grandes cantidades de factores de crecimiento aut&oacute;logos, citoquinas y otros mediadores encontradas PRP y el perfil de c&eacute;lulas mononucleares favorable de PRP puede ayudarnos a estimular la cicatrizaci&oacute;n y resolver la inflamaci&oacute;n cr&oacute;nica.

Un informe del caso sobre el uso de plasma rico en plaquetas de liberaci&oacute;n sostenida para el tratamiento de &uacute;lceras cr&oacute;nicas.

The naturally occurring cyclic tetrapeptide, chlamydocin, originally isolated from fungus Diheterospora chlamydosphoria, consists of α-aminoisobutyric acid, L-phenylalanine, D-proline and an unusual amino acid (S)-2-amino-8-((S)-oxiran-2-yl)-8-oxooctanoic acid (Aoe) and inhibits the histone deacetylases (HDACs), a class of regulatory enzymes. The epoxyketone moiety of Aoe is the key functional group for inhibition. The cyclic tetrapeptide scaffold is supposed to play important role for effective binding to the surface of enzymes. In place of the epoxyketone group, hydroxamic acid and sulfhydryl group have been applied to design inhibitor ligands to zinc atom in catalytic site of HDACs. In the research for more potent HDAC inhibitors, we replaced the epoxyketone moiety of Aoe with different functional groups and synthesized a series of chlamydocin analogs as HDAC inhibitors. Among the functional groups, methoxymethylketone moiety showed as potent inhibition as the hydroxamic acid. On the contrary, we confirmed that borate, trifruoromethylketone, and 2-aminoanilide are almost inactive in HDAC inhibition.

Evaluation of functional groups on amino acids in cyclic tetrapeptides in histone deacetylase inhibition.

Due to their unique property to migrate to pathological lesions, stem cells are used as a delivery vehicle for therapeutic genes to tumors, especially for glioma. It is critically important to track the movement, localization, engraftment efficiency and functional capability or expression of transgenes of selected cell populations following transplantation. The purposes of this study were to investigate whether 1) intravenously administered, genetically transformed cord blood derived EPCs can carry human sodium iodide symporter (hNIS) to the sites of tumors in rat orthotopic model of human glioma and express transgene products, and 2) whether accumulation of these administered EPCs can be tracked by different in vivo imaging modalities.

Endothelial progenitor cells (EPCs) as gene carrier system for rat model of human glioma.

The authors have investigated the usefulness of in vivo chemical exchange saturation transfer MRI for detecting gliomas using a dual-modality imaging contrast agent.

A nano-sized PARACEST-fluorescence imaging contrast agent facilitates and validates in vivo CEST MRI detection of glioma.

We conducted active surveillance for kala-azar and post-kala-azar dermal leishmaniasis (PKDL) in a population of 24,814 individuals. Between 2002 and 2010, 1,002 kala-azar and 185 PKDL cases occurred. Median PKDL patient age was 12 years; 9% had no antecedent kala-azar. Cases per 10,000 person-years peaked at 90 for kala-azar (2005) and 28 for PKDL (2007). Cumulative PKDL incidence among kala-azar patients was 17% by 5 years. Kala-azar patients younger than 15 years were more likely than older patients to develop PKDL; no other risk factors were identified. The most common lesions were hypopigmented macules. Of 98 untreated PKDL patients, 48 (49%) patients had resolution, with median time of 19 months. Kala-azar patients showed elevated interferon-γ (IFNγ), tumor necrosis factor-α (TNFα), and interleukin 10 (IL-10). Matrix metalloproteinase 9 (MMP9) and MMP9/tissue inhibitor of matrix metalloproteinase-1 (TIMP1) ratio were significantly higher in PKDL patients than in other groups. PKDL is frequent in Bangladesh and poses a challenge to the current visceral leishmaniasis elimination initiative in the Indian subcontinent.

Clinical and immunological aspects of post-kala-azar dermal leishmaniasis in Bangladesh.

Disulfide-rich peptide toxins found in the secretions of venomous organisms such as snakes, spiders, scorpions, leeches, and marine snails are highly efficient and effective tools for novel therapeutic drug development. Venom peptide toxins have been used extensively to characterize ion channels in the nervous system and platelet aggregation in haemostatic systems. A significant hurdle in characterizing disulfide-rich peptide toxins from venomous animals is obtaining significant quantities needed for sequence and structural analyses. Presented here is a strategy for the structural characterization of venom peptide toxins from sample limited (4 ng) specimens via direct mass spectrometry sequencing, chemical synthesis and NMR structure elucidation. Using this integrated approach, venom peptide Tv1 from Terebra variegata was discovered. Tv1 displays a unique fold not witnessed in prior snail neuropeptides. The novel structural features found for Tv1 suggest that the terebrid pool of peptide toxins may target different neuronal agents with varying specificities compared to previously characterized snail neuropeptides.

Sample limited characterization of a novel disulfide-rich venom peptide toxin from terebrid marine snail Terebra variegata.

The measurement of extracellular pH (pHe ) has significant clinical value for pathological diagnoses and for monitoring the effects of pH-altering therapies. One of the major problems of measuring pHe with a relaxation-based MRI contrast agent is that the longitudinal relaxivity depends on both pH and the concentration of the agent, requiring the use of a second pH-unresponsive agent to measure the concentration. Here we tested the feasibility of measuring pH with a relaxation-based dendritic MRI contrast agent in a concentration-independent manner at clinically relevant field strengths. The transverse and longitudinal relaxation times in solutions of the contrast agent (GdDOTA-4AmP)44 -G5, a G5-PAMAM dendrimer-based MRI contrast agent in water, were measured at 3 T and 7 T magnetic field strengths as a function of pH. At 3 T, longitudinal relaxivity (r1 ) increased from 7.91 to 9.65 mM(-1) s(-1) (on a per Gd(3+) basis) on changing pH from 8.84 to 6.35. At 7 T, r1 relaxivity showed pH response, albeit at lower mean values; transverse relaxivity (r2 ) remained independent of pH and magnetic field strengths. The longitudinal relaxivity of (GdDOTA-4AmP)44 -G5 exhibited a strong and reversible pH dependence. The ratio of relaxation rates R2 /R1 also showed a linear relationship in a pH-responsive manner, and this pH response was independent of the absolute concentration of (GdDOTA-4AmP)44 -G5 agent. Importantly, the nanoprobe (GdDOTA-4AmP)44 -G5 shows pH response in the range commonly found in the microenvironment of solid tumors.

Concentration-independent MRI of pH with a dendrimer-based pH-responsive nanoprobe.

Automatic sleep scoring is essential owing to the fact that conventionally a large volume of data have to be analyzed visually by the physicians which is onerous, time-consuming and error-prone. Therefore, there is a dire need of an automated sleep staging scheme.

A decision support system for automatic sleep staging from EEG signals using tunable Q-factor wavelet transform and spectral features.

A hallmark of the tumor microenvironment in malignant tumor is extracellular acidosis, which can be exploited for targeted delivery of drugs and imaging agents. A pH sensitive paramagnetic nanoaparticle (NP) is developed by incorporating GdDOTA-4AmP MRI contrast agent and pHLIP (pH Low Insertion Peptide) into the surface of a G5-PAMAM dendrimer. pHLIP showed pH-selective insertion and folding into cell membranes, but only in acidic conditions. We demonstrated that pHLIP-conjugated Gd44-G5 paramagnetic nanoparticle binds and fuses with cellular membrane at low pH, but not at normal physiological pH, and that it promotes cellular uptake. Intracellular trafficking of NPs showed endosomal/lysosomal path ways.

pH-Dependent Cellular Internalization of Paramagnetic Nanoparticle.

Automatic sleep staging is essential for alleviating the burden of the physicians of analyzing a large volume of data by visual inspection. It is also a precondition for making an automated sleep monitoring system feasible. Further, computerized sleep scoring will expedite large-scale data analysis in sleep research. Nevertheless, most of the existing works on sleep staging are either multichannel or multiple physiological signal based which are uncomfortable for the user and hinder the feasibility of an in-home sleep monitoring device. So, a successful and reliable computer-assisted sleep staging scheme is yet to emerge.

Mohammed Bhuiyan

Department of Radiology

The University of Chicago

Automated Radiochemical Synthesis of [¹⁸F]3F4AP: A Novel PET Tracer for Imaging Demyelinating Diseases

Mohammed Bhuiyan

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Radiology

The University of Chicago

Automated Radiochemical Synthesis of [18F]3F4AP: A Novel PET Tracer for Imaging Demyelinating Diseases

Department of Radiology

Automated Radiochemical Synthesis of [¹⁸F]3F4AP: A Novel PET Tracer for Imaging Demyelinating Diseases