19 research outputs found
Interoperabilidad HL7 con un sistema de laboratorio externo
Se presenta la implementación de una plataforma de interoperabilidad entre el sistema de información de SUAT (SIGS) y el Laboratorio de Análisis Clínicos Biofast para la gestión de la solicitud de exámenes desde la indicación en la Historia Cínica Electrónica (HCE), el agendamiento del usuario, la recolección de las muestras, el envío de la solicitud y la posterior recepción de los resultados e integración a la HCE.Sociedad Argentina de Informática e Investigación Operativ
Interoperabilidad HL7 con un sistema de laboratorio externo
Se presenta la implementación de una plataforma de interoperabilidad entre el sistema de información de SUAT (SIGS) y el Laboratorio de Análisis Clínicos Biofast para la gestión de la solicitud de exámenes desde la indicación en la Historia Cínica Electrónica (HCE), el agendamiento del usuario, la recolección de las muestras, el envío de la solicitud y la posterior recepción de los resultados e integración a la HCE.Sociedad Argentina de Informática e Investigación Operativ
A Bowman–Birk protease inhibitor purified, cloned, sequenced and characterized from the seeds of <i>Maclura pomifera</i> (Raf.) Schneid
A new BBI-type protease inhibitor with remarkable structural characteristics was purified, cloned, and sequenced from seeds of Maclura pomifera, a dicotyledonous plant belonging to the Moraceae family.
In this work, we report a Bowman–Birk inhibitor (BBI) isolated, purified, cloned, and characterized from Maclura pomifera seeds (MpBBI), the first of this type from a species belonging to Moraceae family. MpBBI was purified to homogeneity by RP-HPLC, total RNA was extracted from seeds of M. pomifera, and the 3′RACE-PCR method was applied to obtain the cDNA, which was cloned and sequenced. Peptide mass fingerprinting (PMF) analysis showed correspondence between the in silico-translated protein and MpBBI, confirming that it corresponds to a new plant protease inhibitor. The obtained cDNA encoded a polypeptide of 65 residues and possesses 10 cysteine residues, with molecular mass of 7379.27, pI 6.10, and extinction molar coefficient of 9105 M⁻¹ cm⁻¹. MpBBI inhibits strongly trypsin with Kᵢ in the 10⁻¹⁰ M range and was stable in a wide array of pH and extreme temperatures. MpBBI comparative modeling was applied to gain insight into its 3D structure and highlighted some distinguishing features: (1) two non-identical loops, (2) loop 1 (CEEESRC) is completely different from any known BBI, and (3) the amount of disulphide bonds is also different from any reported BBI from dicot plants.Centro de Investigación de Proteínas VegetalesInstituto Multidisciplinario de Biología Celula
A Bowman-Birk protease inhibitor purified, cloned, sequenced and characterized from the seeds of Maclura pomifera (Raf.) Schneid
A new BBI-type protease inhibitor with remarkable structural characteristics was purified, cloned, and sequenced from seeds of Maclura pomifera , a dicotyledonous plant belonging to the Moraceae family. In this work, we report a Bowman-Birk inhibitor (BBI) isolated, purified, cloned, and characterized from Maclura pomifera seeds (MpBBI), the first of this type from a species belonging to Moraceae family. MpBBI was purified to homogeneity by RP-HPLC, total RNA was extracted from seeds of M. pomifera, and the 3'RACE-PCR method was applied to obtain the cDNA, which was cloned and sequenced. Peptide mass fingerprinting (PMF) analysis showed correspondence between the in silico-translated protein and MpBBI, confirming that it corresponds to a new plant protease inhibitor. The obtained cDNA encoded a polypeptide of 65 residues and possesses 10 cysteine residues, with molecular mass of 7379.27, pI 6.10, and extinction molar coefficient of 9105 M-1 cm(-1). MpBBI inhibits strongly trypsin with K (i) in the 10(-10) M range and was stable in a wide array of pH and extreme temperatures. MpBBI comparative modeling was applied to gain insight into its 3D structure and highlighted some distinguishing features: (1) two non-identical loops, (2) loop 1 (CEEESRC) is completely different from any known BBI, and (3) the amount of disulphide bonds is also different from any reported BBI from dicot plants.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)CYTEDCONICETPHusisTherapeutics, 3210 Merryfield Row, San Diego, CA 92121 USAUniv Nacl La Plata, Fac Ciencias Exactas, Ctr Invest Proteinas Vegetales, RA-1900 La Plata, Buenos Aires, ArgentinaUniv Fed Sao Paulo, Dept Biofis, BR-04044020 Sao Paulo, BrazilUniv Autonoma Barcelona, IBB, E-08193 Barcelona, SpainUniv Nacl Arturo Jauretche, Inst Ciencias Salud, 1888 Florencio Varela, Buenos Aires, DF, ArgentinaCITEC, Gonnet, B1897, Buenos Aires, DF, ArgentinaInst Multidisciplinar Biol Celular IMBICE, Lab Neurofisiol, B1906APO, Buenos Aires, DF, ArgentinaUniv Fed Sao Paulo, Dept Biofis, BR-04044020 Sao Paulo, BrazilFAPESP: 12/50191-4RCYTED: Red tematica PROMAL 210RT0398CONICET: PIP 0297Web of Scienc
Rapid and sustained antidepressant properties of an NMDA antagonist/monoamine reuptake inhibitor identified via transporter-based virtual screening
Rational design of lead compounds targeting monoamine transporters (MATs) is critical to developing novel therapeutics to treat psychiatric disorders including depression and substance abuse. A 3-D dopamine transporter (DAT) computer model was used to virtually screen a commercially available small molecule library for high DAT affinity drug-like compounds. One hit, coded MI-4 , inhibited human dopamine, norepinephrine, and serotonin transporters in vitro. In vivo administration in mice induced robust, dose-dependent antidepressant-like behaviors in learned helplessness models (tail suspension and forced swim tests). Moreover, chronic administration (21day, 10mg/kg, bid) reduced drinking latencies comparable to fluoxetine (10mg/kg, bid) in the novelty-induced hypophagia test, which requires chronic treatment to produce antidepressant-like effects. MI-4 (10mg/kg, bid) produced rapid (three-day) antidepressant-like effects in the social avoidance test following 10days of social defeat stress. Unlike ketamine, chronic administration of MI-4 increased social interaction scores while improving resiliency to the mood-altering effects of stress to over 70%. Importantly, MI-4 exhibited minimal abuse liability in behavioral and neurological models (conditioned place preference and dopamine in vivo microdialysis). MI-4 was found to be Ro-25-6981, an ifenprodil analog and reputed NMDA antagonist. The data suggest that Ro-25-6981, previously known for rapid-acting glutamatergic antidepressant actions, may also functionally inhibit monoamine reuptake and produces sustained antidepressant effects in vivo. This demonstrates, as proof of principle, the viability of combining these mechanisms to produce rapid and sustained antidepressant-like effects. Overall, these findings suggest MAT computational model-based virtual screening is a viable method for identifying antidepressant lead compounds of unique scaffold
Azido-iodo-N-benzyl derivatives of threo-methylphenidate (Ritalin, Concerta): Rational design, synthesis, pharmacological evaluation, and dopamine transporter photoaffinity labeling
In contrast to tropane-based compounds such as benztropine and cocaine, non-tropane-based photoaffinity ligands for the dopamine transporter (DAT) are relatively unexplored. Towards addressing this knowledge gap, ligands were synthesized in which the piperidine nitrogen of 3- and 4-iodomethylphenidate was substituted with a benzyl group bearing a photoreactive azide. Analog (±)-3a demonstrated modest DAT affinity and a radioiodinated version was shown to bind covalently to rat striatal DAT and hDAT expressed in cultured cells. Co-incubation of (±)-3a with nonradioactive D-(+)-methylphenidate or (−)-2-β-carbomethoxy-3-β-(4-fluorophenyl)tropane (β-CFT, WIN-35,428, a cocaine analog) blocked DAT labeling. Compound (±)-3a represents the first successful example of a DAT photoaffinity ligand based on the methylphenidate scaffold. Such ligands are expected to assist in mapping non-tropane ligand-binding pockets within plasma membrane monoamine transporters