Different processed products of Polygonati Rhizoma treat Alzheimer's disease in rats: urine metabolomics based on UPLC-Q/TOF-MS / 中国中药杂志

The study investigated the effects of different processed products of Polygonati Rhizoma(black bean-processed Polygonati Rhizoma, BBPR; stewed Polygonati Rhizoma, SPR) on the urinary metabolites in a rat model of Alzheimer's disease(AD). Sixty SPF-grade male SD rats were randomized into a control group, a model group, a donepezil group, a BBPR group, and a SPR group, with twelve rats in each group. Other groups except the control group were administrated with D-galactose injection(100 mg·kg~(-1)) once a day for seven weeks. The control group was administrated with an equal volume of normal saline once a day for seven consecutive weeks. After three weeks of D-galactose injection, bilateral hippocampal Aβ_(25-35) injections were performed for modeling. The rats were administrated with corresponding drugs(10 mL·kg~(-1)) by gavage since week 2, and the rats in the model and control group with an equal volume of double distilled water once a day for 35 continuous days. The memory behaviour and pathological changes in the hippocampal tissue were observed. The untargeted metabolites in the urine were detected by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q/TOF-MS). Principal component analysis(PCA) and orthogonal partial least square-discriminant analysis(OPLS-DA) were employed to characterize and screen differential metabolites and potential biomarkers, for which the metabolic pathway enrichment analysis was conducted. The results indicated that BBPR and SPR increased the new object recognition index, shortened the escape latency, and increased the times of crossing the platform of AD rats in the Morris water maze test. The results of hematoxylin-eosin(HE) staining showed that the cells in the hippocampal tissue of the drug administration groups were closely arranged. Moreover, the drugs reduced the content of interleukin-6(IL-6, P<0.01) and tumor necrosis factor-α(TNF-α) in the hippocampal tissue, which were more obvious in the BBPR group(P<0.05). After screening, 15 potential biomarkers were identified, involving two metabolic pathways: dicoumarol pathway and piroxicam pathway. BBPR and SPR may alleviate AD by regulating the metabolism of dicoumarol and piroxicam.

A study of Slide Positivity Rate (SPR) in three Districts of the Bastar Region of Chhattisgarh State

In Dantewada and Kanker Districts, the SPR began to rise between the 2019-20 and 2020-21 periods, despite the third phase “Malaria-Mukt Bastar Abhiyan” conducted during December 2020 and January 2021. However, in Narayanpur District, it was seen that the SPR came down following the third phase campaign. It remains to be seen as to what the effect of the Phase 4 campaign on the SPRs of Dantewada, Kanker, and Narayanpur would be. This would be possible once the SPR values for 2021-22 are available for these districts.

Celastrol exerts anti-colorectal cancer effect via STAT3 inhibition / 中国药理学通报

Aim To investigate the anti-tumor effect of celastrol(CEL)on colorectal cancer and the possible targets/mechanisms. Methods The cytotoxic activities of CEL were evaluated against A549, HCT-116, HepG2 by CCK-8 method. Western blotting was used to detect the expression level of STAT3 and its upstream and downstream proteins(JAK2, Survivin, MCL-1)in HCT-116 cells before and after CEL treatment Flow cytometry was applied to assess CEL's apoptosis and cell-cycle arrest effect in HCT-116 cells. SPR detection and molecular docking analysis were performed to further assess the binding ability between CEL and STAT3 protein. Lastly, human colorectal cancer organoid culture was constructed to verify the anti-tumor effect of CEL. Results CEL showed significant cytotoxicity to A549(IC50 = 2.37±0.02 μmol·L-1), HCT-116(IC50 = 1.40±0.21 μmol·L-1)and HepG2(IC50 = 2.52±0.02 μmol·L-1). Additionally, CEL could effectively decrease the level of p-STAT3 and the downstream gene expression of STAT3(Survivin and MCL-1)in a concentration-dependent manner; however, CEL did not affect the total level of STAT3 and upstream kinases JAK2. Moreover, CEL could induce apoptosis of HCT-116 cells concentration-dependently and arrest the cell cycle. According to the SPR analysis, CEL showed a strong binding affinity with the KD value(the equilibrium dissociation constant)of 60.38 μmol·L-1. Molecular docking analysis also suggested that CEL bound to the SH2 domain of STAT3. Lastly, CEL showed much better activity than the positive drug oxaliplatin(L-OHP)on all the colorectal cancer organoids. Conclusions CEL shows a significant anti-colorectal cancer effect, potentially caused by a direct target inhibiting STAT3, inducing apoptosis, and blocking the cell cycle.

Simulation Analysis of Occupancy Rates of Baicalein， Quercetin and Galangin on Target Sites of Xanthine Oxidase / 中国实验方剂学杂志

Objective:To simulate the occupancy rates of baicalein， quercetin and galangin on the target sites of xanthine oxidase <italic>in vivo</italic>. Method:In this experiment， the half inhibitory concentration （IC₅₀） of febuxostat， baicalein， quercetin and galangin against xanthine oxidase were determined by <italic>in vitro</italic> enzymatic reaction. Binding free energy was predicted by molecular docking technology and their association rate constant （k_on） and dissociation rate constant （k_off） were determined by surface plasmon resonance technology. Based on measured binding kinetic parameters （k_on and k_off） and extracted pharmacokinetic data， the target occupancy model <italic>in vivo</italic> was established. Result:The IC₅₀values of febuxostat， baicalein， quercetin and galangin were 0.002 7， 1.63， 0.38， 1.59 µmol·L^-1， respectively. The IC₅₀ of febuxostat was very close to that reported in the literature. The predicted curve of target occupancy rate <italic>in vivo</italic> of febuxostat was consistent with its duration of clinical efficacy. When single intragastric administration of long-circulating liposomes of quercetin with dose of 100 mg·kg^-1 in rats， the time of target occupancy rate >70% <italic>in vivo</italic> lasted for about 3.9 h. When rats were orally administered baicalein and galangin with dose of 200 mg·kg^-1， the time of target occupancy rate >50% <italic>in vivo </italic>lasted for about 10 h and 1.7 h， respectively. Conclusion:The prediction model of xanthine oxidase target occupancy constructed by drug target binding kinetics and <italic>in vivo</italic> pharmacokinetic curves can effectively evaluate the <italic>in vivo</italic> inhibitory activity of compounds against the target.

Efectividad y seguridad de la vacuna Sarampión-Paperas-Rubéola (SPR) en mayores de cinco años / Effectiveness and safety of the Measles-Mumps-Rubella vaccine (SPR) in over five years

ANTECEDENTES: La inmunización es una de las intervenciones en salud pública más costo efectivas y rentables. Sarampión, parotiditis y rubeola (SPR) son enfermedades virales, que pueden causar complicaciones y consecuencias graves, especialmente en niños desnutridos e inmunodeprimidos; siendo importante destacar, que estas enfermedades son prevenibles mediante la vacunación. El resurgimiento de las infecciones por el virus de las paperas entre personas previamente vacunados con dos dosis, ha planteado preocupaciones en el mundo, sobre la ausencia de inmunidad a largo plazo después de la vacunación contra esta enfermedad y ha aperturado discusiones sobre nuevas estrategias para mitigar el riesgo de brotes futuros, incluyendo la posibilidad de implementar una tercera dosis de la vacuna SPR como respuesta a un brote epidémico, frente al cual, además surge la necesidad de estudios adicionales que evalúen la protección a largo plazo proporcionada por tres dosis de las vacunas SPR, así como la rentabilidad de la implementación de ésta intervención. OBJETIVO: El objetivo de la presente revisión sistemática es sintetizar evidencias científicas sobre la seguridad y efectividad frente a parotiditis de la vacuna Sarampión, Rubéola, Paperas (SPR) en personas mayores de 5 años. METODOLOGÍA: La búsqueda sistemática se realizó en la base de datos de Medline (PubMed), Lilacs y Cochrane Library fueron formuladas una estrategia de búsqueda para la pregunta PICO de la revisión, no se aplicaron filtros de fecha ni idiomas, la búsqueda abordó la evidencia publicada hasta 12 de marzo del 2020. La selección de título y resumen y extracción de datos fue realizada por un solo revisor. RESULTADOS: La búsqueda identificó 9 estudios: 1 revisión sistemática, 1 ensayo clínico y 7 estudios observacionales. La revisión incluyó tres estudios en niños y adolescentes. El ensayo clínico se realizó en adultos y los estudios observacionales fueron en adultos y en niños. CONCLUSIONES: No se observan diferencias estadísticamente significativas entre los niños que reciben una tercera dosis con los que reciben dos dosis. La vacuna SPR en niños mayores de 5 años presenta pocos y leves reacciones adversas. En adultos sanos, la tercera dosis de SPR no presenta reacciones adversas graves o largo plazo. En población militar, la aplicación de vacuna SPR no se asocia con aparición de diabetes mellitus tipo 1. (AU)

Identification of PD-1 small molecule inhibitors and validation in Panax ginseng / 药学学报

Tumor immune therapy has been remarkably successful in recent years and several kinds of PD-1/PD-L1 (programmed death-1/programmed death-ligand 1) antibody drugs have been approved by the FDA for treatment of advanced malignant neoplasms. However, as biomacromolecules these antibody drugs have certain drawbacks such as high cost, injection-only administration and immunogenicity; thus, we turned to small molecules that have lower immune risks and better modifiability. Considering the structural diversity of natural products, we chose to investigate the active components in Panax ginseng, a famous and highly valued traditional Chinese medicine. Nine compounds were separated and identified in this research using a HPLC-coupled MS system, and 3 PD-1 binding compounds were identified using the SPR method. The PD-1/PD-L1 inhibitory ability of ginsenoside Rg1, as a representative ginsenoside, was verified by cytopharmacological methods. This research provides a new method for the identification of immune blockade inhibitors in natural products.

Meningitis aguda posterior a vacuna tresvírica / Acute meningitis following mumps vaccine

Resumen En Chile, la cepa del virus parotídeo utilizada en la vacuna es Leningrad-Zagreb (L-Z). Aunque la relación entre meningitis y la cepa L-Z sigue siendo controvertida, la mayoría de los casos reportados han presentado un cuadro de curso benigno y sin secuelas neurológicas. Presentamos el caso de una paciente que tres semanas post-inmunización con la vacuna tresvírica evolucionó con una meningitis aséptica de predominio mononuclear, con serología para IgM positiva contra el virus parotídeo. En este caso clínico, existió una relación temporal entre la vacunación, el inicio del cuadro parotídeo y posteriormente el meníngeo; la curva de inmunoglobulinas demostró una infección aguda posterior a la vacuna. Si bien no se logró aislar el virus en LCR, es razonable atribuir el cuadro a una infección post-vacunal.

In Chile, the strain of the mumps virus used in the vaccine is Leningrad-Zagreb (L-Z). Although the relationship between meningitis and the L-Z strain remains controversial, most of the reported cases have shown a benign course without permanent neurological sequelae. We present a case of a patient who presented an aseptic meningitis three weeks after immunization with a mumps vaccine; and laboratory confirmation showed positive serum mumps IgM antibody. In this clinical case, there was a temporal relationship between vaccination and the onset of the mumps and subsequently the meningeal involvement; the immunoglobulin curve demonstrates acute infection after vaccination. Although it was not possible to isolate the virus in CSF, it is reasonable to attribute the picture to a post-vaccinal infection.

Screening of 14-3-3τ protein inhibitors from natural products based on fluorescence spectroscopy, surface plasmon resonance and molecular docking technique / 国际药学研究杂志

Objective:To study and establish a method for the efficient screening of 14-3-3τ protein inhibitors from natural products, and analyze the sites of their interactions with the 14-3-3τ protein. Methods: The binding activity of natural compounds with the 14-3-3τ protein was tested by the liquid chromatography-fluorescence spectroscopy, and the binding activity of the potential compounds was further verified by the surface plasmon resonance(SPR)technique. The binding sites of the active compounds were predicted by the molecular docking technique. Furthermore, the key binding sites were selected and then validated using amino acid site-directed mutants. Results: A total of 17 different type compounds with potential 14-3-3τ binding activity were screened out from 82 natural products. The binding activi- ties of 10 compounds were verified by the SPR experiments. Then the binding sites of interactions between the 14-3-3τ protein and the 10 compounds were predicted by the molecular docking technology to be mainly at the Arg56, Arg127 and Y128A, dem- onstrate that the binding of five of the 10 compounds with the target protein was associated with the three sites Arg56, Arg127 and Tyr128. Conclusion: The established method is accurate and efficient, which could be used for rapid screening of small molecule 14-3-3τ inhibitors from natural products. The present study provides a reference and a new approach for the rapid screening of 14-3-3τ inhibitors for the new breast cancer therapeutic drugs.

Application of surface plasmon resonance biosensor in quantitative analysis re-search / 药学实践杂志

Surface plasmon resonance(SPR) is an optical phenomenon arises from mass changes on sensors based on in-teraction between substances ,which could monitor the interaction between biomolecules quickly and accurately .It has the ad-vantage of label-free ,high specificity ,high accuracy ,real-time and on-line monitoring ,which has attracted comprehensive at-tention in recent years .SPR biosensors could be applied in drug discovery ,clinical diagnosis ,food safety ,environment monito-ring and proteomics .In this manuscript ,the application of SPR biosensors in food safety ,environment monitor and biomedical analysis have been reviewed ,which could provide reference to related research .

Z1, a novel DENV2 NS5 RdRp small molecular inhibitor, inhibits DENV2 replication and infection / 中国药理学通报

Aim To screen novel NS5 inhibitors a-gainst dengue virus ( DENV) replication. Methods His-tagged DENV2 NS5 RNA-dependent polymerase ( NS5 RdRp ) was expressed and purified in BL21 cells. The binding ability of the small molecules to NS5 polymerase was determined by SPR assay. The activity of dengue inhibition by Z1 was determined by CPE, LDH and plaque assay. RNA synthesis was as-sessed by Real-time PCR. The dsRNA synthesis and viral proteins were detected by immunofluorescence as-say. The level of viral proteins was examined by West-ern blot. The stage of DENV life cycle was evaluated by time of drug-addition assay. Results A small mo-lecular Z1 was discovered, which could bind to NS5 RdRp. Z1 inhibited DENV2 RNA replication, synthe-sis of dsRNA and protein synthesis in post-entry stage of dengue life-cycle. Cell based assay confirmed that Z1 inhibited DENV-induced cell death with EC50 val-ues of 4. 75μmol·L-1 . Conclusions The novel NS5 inhibitor Z1, inhibits DENV2 RNA replication, protein synthesis and release of progeny virus, which may be severed as an anti-DENV2 antiviral drug for further de-velopment.

Overview of the detection methods for equilibrium dissociation constant KD of drug-receptor interaction / 药物分析学报

Drug-receptor interaction plays an important role in a series of biological effects, such as cell pro-liferation, immune response, tumor metastasis, and drug delivery. Therefore, the research on drug-re-ceptor interaction is growing rapidly. The equilibrium dissociation constant (KD) is the basic parameter to evaluate the binding property of the drug-receptor. Thus, a variety of analytical methods have been established to determine the KD values, including radioligand binding assay, surface plasmon resonance method, fluorescence energy resonance transfer method, affinity chromatography, and isothermal ti-tration calorimetry. With the invention and innovation of new technology and analysis method, there is a deep exploration and comprehension about drug-receptor interaction. This review discusses the differ-ent methods of determining the KD values, and analyzes the applicability and the characteristic of each analytical method. Conclusively, the aim is to provide the guidance for researchers to utilize the most appropriate analytical tool to determine the KD values.

The application of SPR technology in prenatal testing of fetal RHD blood type gene / 国际检验医学杂志

Objective To study the feasibility of detecting fetus RhD type gene by Surface Plasmon Reso-nance(SPR)technology,and to establish a new rapid diagnosis method for fetus RhD type gene.Methods The different types of DNA corresponding RNA probes were fixed on the surface of SPR chip by using amino cou-pling methods,and optimize the chip analysis condition,and then using the RNase H enzyme hydrolysis,signal amplification detection,at last the detection conditions were determined.We use the RhD type gene exon 5,7 of RNA probe to test its corresponding DNA molecules,and analyse the specificity and sensitivity of SPR chip detection signal.Results The SPR technique for detecting the exon 5,7 of RhD blood type gene shows good sensitivity and specificity in all,SPR technology can specifically detect the Exon 5,7 of RhD blood type gene, and the sensitivity of for detecting RhD gene exon 5,7 is 100 pmol/L by SPR.Conclusion The SPR technolo-gy can quickly detect RhD gene accordingly,SPR technology is simple,rapid,reliable and label-free,w hich can provide a new way predicting fetal RhD type for RhD negative prenatal.

Polymer-based surface plasmon resonance biochip: construction and experimental aspects

Abstract Introduction: Surface plasmon resonance biosensors are high sensitive analytical instruments that normally employ glass materials at the optical substrate layer. However, the use of polymer-based substrates is increasing in the last years due to favorable features, like: disposability, ease to construction and low-cost design. Review Recently, a polymer-based SPR biochip was proposed by using monochromatic and polychromatic input sources. Its construction and experimental considerations are detailed here. Experimental considerations and results, aspects from performance characteristics (resonance parameters, sensitivity and full width at half maximum – FWHM – calculations) are presented for hydrophilic and hydrophobic solutions. It is included also a brief description of the state of the art of polymer-based SPR biosensors.

Gold Nanoparticles synthesis, properties, and forthcoming applications – A review .

Gold nanoparticles (AuNPs) have several biomedical applications in diagnosis and treating of disease such as targeted chemotherapy and in pharmaceutical drug delivery due to their multifunctionality and unique characteristics. AuNPs can be conjugated with ligands, imaging labels, therapeutic drugs and other functional moieties for site specific drug delivery application. In this present review we are discussing the synthesis, properties, and forthcoming applications of gold nanoparticle (AuNPs) which is the most studied among all other metallic-nanoparticles. Here our main focus is to explain the AuNPs application in cancer treatment. AuNPs provides non-toxic carrier system for pharmaceutical drug and gene delivery applications. Currently various anticancer drugs are available but these are cause the necrosis of cancerous cell as well as normal cells. AuNPs cause the necrosis of only cancer cells therefore we can utilize it as a delivery vehicle as well as anticancer agent.

Detection of platelet antibody by surface plasmon resonance technique and its preliminary application / 重庆医学

Objective To study the platelet antibody screening and crossing match by surface plasmon resonance(SPR) ,and to find a new way for platelet compatibility testing .Methods The corresponding universal platelet antigen was fixed on the SPR chip surface by the amino coupling method .Platelet antibody positive and negative control serum were analysed by SPR micro-ar-ray ,the stability ,sensitivity and specificity of this technique were discussed ,and compared with MAIPA assay .Finally we used the SPR technology to cross match for ten cases of the platelet antibody positive patients before infusion ,and to evaluate the effect of platelet infusion .Results For the SPR technology ,the stability ,sensitivity and specificity of platelet antibody detection were all better ,106 cases of the repeated platelet transfusion samples were tested by SPR assay and MAIPA method ,there was no signifi-cant difference between them(chi-square=0 .333 ,P>0 .05) ,the total consistency was 97 .2% .The 10 cases of platelet antibody positive patients were crossed match before platelet transfusion by SPR technology ,the good results of 8 cases of them were found by the clinical tracking evaluation ,1 h CCI>7 .5 ,24 h CCI>4 .5 .Conclusion SPR technology for screening platelet antibody mat-ches with MAIPA method in basic quality ,but SPR assay is simple ,rapid ,reliable and intuitive ,label free ,which can satisfy the re-quirements for clinical rapid detection of platelet antibody screening and crossing match .

Clinic research into the effects of SPR on the sensory function of lower extremities / 中华显微外科杂志

Objective To explore the reason why the SPR could make the changes of Sensory Function of Lower extremities,and the clinical significance of these changes.Methods From February,2012 to August,2014,24 patients with spastic cerebral palsy who were consistent with the indications of SPR,had normal intelligence development,and express competence,and could cooperate with the test.To test the changes of Sensory Function of lower extremities preoperatively,1 week after SPR,such as haptics,superficial algaesthesis,temperature sensation,cinaesthesia,topesthesia,pallesthesia,deep pain sense,tactile localization sense,two point discrimination and pattern sense.Results There were 6 patients who present with skin paresthesia of lower extremities among the 24 patients after the SPR.Of the 6 patients,4 became normal 2 weeks later,1 became normal 3 weeks later,and the longest 1 became normal 6 weeks later.No instances with permanent sensory deprivation and anaesthesia were found.The proportions of the excised root of spinal nerves during the SPR in the groups with skin anaesthesia of lower extremities and without skin anaesthesia of lower extremities were 0.268 ± 0.049 and 0.193 ± 0.074 (P ＜ 0.05 respectively).The former was significantly higher than the latter.The changes of haptics,cinaesthesia,topesthesia,deep pain sense,tactile localization sense,two point discrimination,pallesthesia preoperatively,1 week after SPR were not significantly different (P ＞ 0.05).There were significant differences in the superficial algaesthesis,pattern sense and temperature sensation preoperatively and postoperatively (P ＜ 0.05).Both of them decreased compared with those of 1 week after SPR.Conclusion The slight damage to sensory function of lower extremities resulted from SPR may not affect the protectant sensory function of the body.The skin anaesthesia of lower extremities is probably concerned with the proportion of the excised root of spinal nerves during the SPR,but not associated with the age.The impaired symptoms of the sensory function of lower extremities resulted from SPR can spontaneous recover in 2-6 weeks after SPR.SPR is safely with the clinic research on the sensory function of lower extremities.

Trends of malaria situation in Jamnagar District.

Introduction: Five out of eight districts of Saurashtra region are declared hyper endemic for malaria in the year 2011-12 & 2012-13 and given priority by World Bank Project for Malaria control activity in these districts. Burden of malaria contributed by these districts is more than 40% of total burden of Gujarat state, and Jamnagar is one of those districts. By Studying trend of Malaria in Jamnagar district will give an opportunity to identify particular seasonal trends and thus by effective surveillance mechanism, future out-breaks can be prevented. Aim & Objectives: 1) To study the trend of malaria situation in various Talukas of Jamnagar District. 2) To compare the trends for last four years. Materials & Method: Present record base study was carried out in 10 Talukas of Jamnagar district to analyzed the trend of malaria situation in the Jamnagar district by department of community medicine, Shri M.P.Shah Medical College, Jamnagar during the month of September 2012 to analyze the trend from the year 2009 to 2012 (up to September month). This was based on the monthly and progressive data format (monthly reports) was collected form District Malaria Officer of Jamnagar district and analyzed by using Microsoft excel 2007 and the result was presented in Table and graph. Results: Total numbers of cases were decreasing over the period of last 3 years. ABER is >10% in most of the Talukas which is indicated the surveillance activity is done properly over the period of years. Conclusion: In the year 2012 all parasitological indicators showing decreasing trend of malaria in comparison with previous years i.e. API, ABER, SPR, PF, and no malarial deaths at all. Continuous surveillance is effective in reduce the morbidity and mortality of vector borne disease like malaria. Seasonal trend of malaria follows the same pattern of distribution showing peak in months of Jun-July.

FGF2 de 18kDa e de 22.5kDa: sinalização molecular parácrina e funções biológias / FGF2 species of 18 and 22.5 kDa: paracrine molecular signaling and biological functions

FGF2 (Fibroblast Growth Factor 2), o fundador da família FGF, tem funções regulatórias na mitogênese, diferenciação, morfogênese e reparo tecidual. Diversas espécies moleculares de FGF2 compartilham uma seqüência C-terminal comum de 155 aminoácidos, pois se originam de diferentes sítios de iniciação de leitura de um único mRNA. O menor, o FGF2-18kDa, é liberado extracelularmente para se ligar a receptores específicos (FGFRs) para disparar as funções parácrinas e autócrinas pelas quais este fator é conhecido. Por outro lado, as espécies maiores (FGF2-21, 22, 22,5 e 34kDa) são intracelulares se ligam a parceiros moleculares desconhecidos para exercer funções intrácrinas ainda indefinidas. O objetivo desta tese foi produzir espécies recombinantes do FGF2-18 e FGF2-22,5, na forma de proteínas de fusão, para analisar funções biológicas e mecanismos de sinalização. Nas células malignas Y1 de camundongo, os recombinantes de FGF2-18kDa (FGF2-18, His-FGF2-18 e His-FGF2-18-ProA) dispararam uma resposta antagônica estimulando as vias de sinalização mitogênica, mas bloqueando o ciclo celular. Nos fibroblastos não tumorigênicos Balb3T3, estes mesmos recombinantes de FGF2-18kDa dispararam apenas a resposta mitogênica clássica. Todos os efeitos biológicos destes recombinantes de FGF2-18kDa foram bloqueados pelo inibidor específico da proteína quinase de tirosina dos FGFRs, PD173074, demonstrando que são respostas intermediadas pelos FGFRs. Portanto, os domínios estruturais adicionados aos recombinantes de FGF2-18kDa não impediram que estas proteínas se ligassem e ativassem os FGFRs. Por outro lado, o recombinante His-FGF2-22,5 dispara apenas as vias de sinalização mitogênica em ambas as células Y1 e 3T3, mas este efeito biológico não é inibido por PD173074. Estes resultados sugerem que a seqüência N-terminal de 55 resíduos, rica em aminoácidos básicos, impede que o FGF2-22,5kDa se ligue e/ou ative os FGFRs. Entretanto, o recombinante His-FGF2-22,5ProA dispara a resposta...

FGF2 (Fibroblast Growth Factor 2), the founder of the FGF family, has regulatory functions in mitogenesis, differentiation, morphogenesis and tissue repair. Multiple FGF2 molecular species, sharing a C-terminal sequence of 155 amino acids, are translated from different iniciation sites of the same mRNA. The smaller, the FGF2-18kD, is extracellularly released to bind to specific membrane receptors (FGFRs), performing paracrine and autocrine functions. On the other hand, the larger FGF2s (21, 22, 22.5 and 34kDa) are intracellular species that bind to unknown partners to play still undefined intracrine roles. The aim of this thesis was to produce recombinant species of FGF2-18kDa and FGF2-22,5kDa, in the form of fusion proteins, to analyze functions and signaling mechanisms. In mouse Y1 malignant cells, FGF2-18kD recombinants (FGF2-18kDa and His-FGF2-18kDaProA) triggered an antagonistic response activating mitogenic signaling pathways, but blocking the cell cycle. However, in non tumorigenic Balb3T3 fibroblasts, these same FGF2-18kD recombinants only elicited the classical mitogenic response. All biological effects of these FGF2-18kD recombinants were blocked by the specific inhibitor of FGFR-protein-tyrosine-kinases, PD173074, demonstrating that these responses are mediated by FGFRs. Therefore, the new peptide domains added to FGF2-18kD did not prevent these recombinant fusion proteins to bind and activate FGFRs. Conversely, the recombinant His-FGF2-22,5kDa triggered only mitogenic signaling pathways in both Y1 and Balb3T3 cells, a biological effect not inhibited by PD173074. These results suggested that the additional basic-rich N-terminal sequence of 55 amino acid residues, found in FGF2-22,5kDa, prevents this FGF2 species from binding and / or activate FGFRs. However, surprisingly, the recombinant His-FGF2-22kDaProA triggered the antagonistic response characteristic of FGF2-18kDa. These results imply that the ProA-domain added to the C-terminal end...

Effect of Neostigmine on Cardiovascular Response from Neuromuscular Electrical Stimulation in Selective Posterior Rhizotomy for Patients with Cerebral Palsy / 中国康复理论与实践

@#Objective To observe the effect of intravenous pre-injection of neostigmine on cardiovascular response(CVR) caused by neuromuscular electrical stimulation(NMES) in selective posterior rhizotomy(SPR) for patients with cerebral palsy.Methods 56 patients with cerebral palsy undergoing SPR at lumbarsacral segments under general anesthesia were randomly assigned to 2 groups: intravenous neostigmine 0.04 mg/kg(no more than 1 mg in total) and intravenous atropine 0.02 mg/kg(no more than 0.5 mg in total) 5 min before NMES in group N,and intravenous normal saline 0.12 ml/kg instead in group C.The systolic blood pressure(SBP) and heart rate(HR) at following time points: before skin incision(T1),before intravenous neostigmine/atropine or normal saline injection(T2),1 min after NMES(T3),and 10 min after NMES(T4).Results SBP and HR at T3 in group N were significantly lower than those in group C(P<0.01).No significant difference was found at T1,T2 and T4 between two groups(P>0.05).Cases who needed extra dose of fentanyl during NMES in group N were significantly lower than those in group C(P<0.01).Conclusion Intravenous pre-injection of neostigmine before NMES can effectively decrease the CVR caused by NMES.

Verbal Memory Function and Characteristics of Memory Process in Schizophrenia and Affective Disorder

OBJECTIVES: This study was to compare verbal memory ability among patients with schizophrenia, bipolar manic patients and unipolar depressive patients, and to understand their charicteristics of memory process. METHODS: All subjects were hospitalized patients and had been interviewed by using the Structured Clinical Interview for DSM-IV(SCID). Schizophrenic patients(N=40), bipolar manic patients(N=17), and unipolar depressive patients(N=20) were assessed with K-AVLT for verbal memory and with K-WAIS for verbal IQ. Three groups were compared regarding total immediate recall, delayed recall, delayed recognition, learning curve, memory retention, and retrieval efficiency under controlled verbal IQ. Multiple regression analysis was performed to find which clinical factors have an influence on verbal memory ability. RESULTS: In MANCOVA, differences of verbal memory test scores among the groups were statistically significant(F=1.800, p<.05). In post hoc analysis, Patients with schizophrenia and bipolar mania showed poorer performance in immediate recall, delayed recall, delayed recognition, retrieval efficiency than unipolar depressive patients. And schizophrenics performed poorly in delayed recall, delayed recognition, retrieval efficiency than nonpsychotic affective disorder group, but no difference in total immediate recall, delayed recall, delayed recognition, retrieval efficiency between the schizophrenic group and the psychotic affective group. CONCLUSIONS: These results partially confirm previous reports of verbal memory ability among major psychiatric disorders. Our results showed that psychotic symptoms were related with verbal memory, and longer duration of illness was related with poorer performance in schizophrenia and unipolar depression.