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1.
Acta Pharmaceutica Sinica B ; (6): 763-780, 2021.
Article in English | WPRIM | ID: wpr-881168

ABSTRACT

Intestinal toxicity induced by chemotherapeutics has become an important reason for the interruption of therapy and withdrawal of approved agents. In this study, we demonstrated that chemotherapeutics-induced intestinal damage were commonly characterized by the sharp upregulation of tryptophan (Trp)-kynurenine (KYN)-kynurenic acid (KA) axis metabolism. Mechanistically, chemotherapy-induced intestinal damage triggered the formation of an interleukin-6 (IL-6)-indoleamine 2,3-dioxygenase 1 (IDO1)-aryl hydrocarbon receptor (AHR) positive feedback loop, which accelerated kynurenine pathway metabolism in gut. Besides, AHR and G protein-coupled receptor 35 (GPR35) negative feedback regulates intestinal damage and inflammation to maintain intestinal integrity and homeostasis through gradually sensing kynurenic acid level in gut and macrophage, respectively. Moreover, based on virtual screening and biological verification, vardenafil and linagliptin as GPR35 and AHR agonists respectively were discovered from 2388 approved drugs. Importantly, the results that vardenafil and linagliptin significantly alleviated chemotherapy-induced intestinal toxicity

2.
Acta Pharmaceutica Sinica B ; (6): 1914-1930, 2021.
Article in English | WPRIM | ID: wpr-888842

ABSTRACT

Overactive bladder (OAB) is the most bothersome symptom in lower urinary tract symptoms (LUTS). Current pharmacologic treatment aims to inhibit detrusor contraction; however, shows unsatisfied efficacy and high discontinuation rate. LIM kinases (LIMKs) promote smooth muscle contraction in the prostate; however, their function in the bladder smooth muscle remains unclear. Here, we studied effects of the LIMK inhibitors on bladder smooth muscle contraction and proliferation both

3.
Acta Pharmaceutica Sinica B ; (6): 2344-2361, 2021.
Article in English | WPRIM | ID: wpr-888806

ABSTRACT

Recent infectious disease outbreaks, such as COVID-19 and Ebola, have highlighted the need for rapid and accurate diagnosis to initiate treatment and curb transmission. Successful diagnostic strategies critically depend on the efficiency of biological sampling and timely analysis. However, current diagnostic techniques are invasive/intrusive and present a severe bottleneck by requiring specialist equipment and trained personnel. Moreover, centralised test facilities are poorly accessible and the requirement to travel may increase disease transmission. Self-administrable, point-of-care (PoC) microneedle diagnostic devices could provide a viable solution to these problems. These miniature needle arrays can detect biomarkers in/from the skin in a minimally invasive manner to provide (near-) real-time diagnosis. Few microneedle devices have been developed specifically for infectious disease diagnosis, though similar technologies are well established in other fields and generally adaptable for infectious disease diagnosis. These include microneedles for biofluid extraction, microneedle sensors and analyte-capturing microneedles, or combinations thereof. Analyte sampling/detection from both blood and dermal interstitial fluid is possible. These technologies are in their early stages of development for infectious disease diagnostics, and there is a vast scope for further development. In this review, we discuss the utility and future outlook of these microneedle technologies in infectious disease diagnosis.

4.
Acta Pharmaceutica Sinica B ; (6): 850-860, 2020.
Article in English | WPRIM | ID: wpr-828839

ABSTRACT

Organic anion transporting polypeptide 1B1 and 1B3 (OATP1B1/3) as important uptake transporters play a fundamental role in the transportation of exogenous drugs and endogenous substances into cells. Rat OATP1B2, encoded by the gene, is homologous to human OATP1B1/3. Although OATP1B1/3 is very important, few animal models can be used to study its properties. In this report, we successfully constructed the S knockout (KO) rat model using the CRISPR/Cas9 technology for the first time. The novel rat model showed the absence of OATP1B2 protein expression, with no off-target effects as well as compensatory regulation of other transporters. Further pharmacokinetic study of pitavastatin, a typical substrate of OATP1B2, confirmed the OATP1B2 function was absent. Since bilirubin and bile acids are the substrates of OATP1B2, the contents of total bilirubin, direct bilirubin, indirect bilirubin, and total bile acids in serum are significantly higher in KO rats than the data of wild-type rats. These results are consistent with the symptoms caused by the absence of OATP1B1/3 in Rotor syndrome. Therefore, this rat model is not only a powerful tool for the study of OATP1B2-mediated drug transportation, but also a good disease model to study hyperbilirubinemia-related diseases.

5.
Acta Pharmaceutica Sinica B ; (6): 1397-1413, 2020.
Article in English | WPRIM | ID: wpr-828800

ABSTRACT

Pyroptosis is a form of programmed cell death, and recently described as a new molecular mechanism of chemotherapy drugs in the treatment of tumors. Miltirone, a derivative of phenanthrene-quinone isolated from the root of Bunge, has been shown to possess anti-cancer activities. Here, we found that miltirone inhibited the cell viability of either HepG2 or Hepa1-6 cells, and induced the proteolytic cleavage of gasdermin E (GSDME) in each hepatocellular carcinoma (HCC) cell line, with concomitant cleavage of caspase 3. Knocking out switched miltirone-induced cell death from pyroptosis to apoptosis. Additionally, the induction effects of miltirone on GSDME-dependent pyroptosis were attenuated by siRNA-mediated caspase three silencing and the specific caspase three inhibitor Z-DEVD-FMK, respectively. Miltirone effectively elicited intracellular accumulation of reactive oxygen species (ROS), and suppressed phosphorylation of mitogen-activated and extracellular signal-regulated kinase (MEK) and extracellular regulated protein kinases 1/2 (ERK1/2) for pyroptosis induction. Moreover, miltirone significantly inhibited tumor growth and induced pyroptosis in the Hepa1-6 mouse HCC syngeneic model. These results provide a new insight that miltirone is a potential therapeutic agent for the treatment of HCC GSDME-dependent pyroptosis.

6.
Article in Chinese | WPRIM | ID: wpr-824926

ABSTRACT

Objective This paper studied the characteristics and contents of the hospital scientific research management subsystem based on HRP system,analyzing its characteristics and functions,proposing solutions to identified problems to improve the hospital management and core competitiveness.Methods Through the analysis of the characteristics and design module contents of the research management subsystem of HRP system,some problems were identified in the system,such as the long adaptation process of researchers' new or old concepts,unstable research management subsystem affecting the links between departments and so on.Results To better deal with identified problems,this paper put forward some improvement measurements,such as strengthening the monitoring of H RP system's scientific research management subsystem,strengthening the safety construction of both HRP system and scientific research management subsystem.Conclusions HRP system and scientific research management subsystem reflect the refinement,scientific and integration of hospital management,which is a hospital management concept and a means to improve the core competitiveness of the hospital.We should change the percep tions,improve understandings,strengthen the collaboration,and promote the overall development of the hospital.

7.
Acta Pharmaceutica Sinica B ; (6): 279-293, 2019.
Article in English | WPRIM | ID: wpr-774986

ABSTRACT

Over recent decades, many studies have reported that hypocrellin A (HA) can eliminate cancer cells with proper irradiation in several cancer cell lines. However, the precise molecular mechanism underlying its anticancer effect has not been fully defined. HA-mediated cytotoxicity and apoptosis in human lung adenocarcinoma A549 cells were evaluated after photodynamic therapy (PDT). A temporal quantitative proteomics approach by isobaric tag for relative and absolute quantitation (iTRAQ) 2D liquid chromatography with tandem mass spectrometric (LC-MS/MS) was introduced to help clarify molecular cytotoxic mechanisms and identify candidate targets of HA-induced apoptotic cell death. Specific caspase inhibitors were used to further elucidate the molecular pathway underlying apoptosis in PDT-treated A549 cells. Finally, down-stream apoptosis-related protein was evaluated. Apoptosis induced by HA was associated with cell shrinkage, externalization of cell membrane phosphatidylserine, DNA fragmentation, and mitochondrial disruption, which were preceded by increased intracellular reactive oxygen species (ROS) generations. Further studies showed that PDT treatment with 0.08 µmol/L HA resulted in mitochondrial disruption, pronounced release of cytochrome , and activation of caspase-3, -9, and -7. Together, HA may be a possible therapeutic agent directed toward mitochondria and a promising photodynamic anticancer candidate for further evaluation.

8.
Acta Pharmaceutica Sinica B ; (6): 675-689, 2019.
Article in English | WPRIM | ID: wpr-774952

ABSTRACT

Erythrocytes (red blood cells, RBCs) are the most abundant circulating cells in the blood and have been widely used in drug delivery systems (DDS) because of their features of biocompatibility, biodegradability, and long circulating half-life. Accordingly, a "camouflage" comprised of erythrocyte membranes renders nanoparticles as a platform that combines the advantages of native erythrocyte membranes with those of nanomaterials. Following injection into the blood of animal models, the coated nanoparticles imitate RBCs and interact with the surroundings to achieve long-term circulation. In this review, the biomimetic platform of erythrocyte membrane-coated nano-cores is described with regard to various aspects, with particular focus placed on the coating mechanism, preparation methods, verification methods, and the latest anti-tumor applications. Finally, further functional modifications of the erythrocyte membranes and attempts to fuse the surface properties of multiple cell membranes are discussed, providing a foundation to stimulate extensive research into multifunctional nano-biomimetic systems.

9.
Acta Pharmaceutica Sinica B ; (6): 960-972, 2019.
Article in English | WPRIM | ID: wpr-774930

ABSTRACT

Monoclonal antibodies (mAbs) are widely used in many fields due to their high specificity and ability to recognize a broad range of antigens. IL-17A can induce a rapid inflammatory response both alone and synergistically with other proinflammatory cytokines. Accumulating evidence suggests that therapeutic intervention of IL-17A signaling offers an attractive treatment option for autoimmune diseases and cancer. Here, we present a combinatorial approach for optimizing the affinity and thermostability of a novel anti-hIL-17A antibody. From a large naïve phage-displayed library, we isolated the anti-IL-17A mAb 7H9 that can neutralize the effects of recombinant human IL-17A. However, the modest neutralization potency and poor thermostability limit its therapeutic applications. affinity optimization was then used to generate 8D3 by using yeast-displayed random mutagenesis libraries. This resulted in four key amino acid changes and provided an approximately 15-fold potency increase in a cell-based neutralization assay. Complementarity-determining regions (CDRs) of 8D3 were further grafted onto the stable framework of the huFv 4D5 to improve thermostability. The resulting hybrid antibody 9NT/S has superior stabilization and affinities beyond its original antibody. Human fibrosarcoma cell-based assays and analyses in mice indicated that the anti-IL-17A antibody 9NT/S efficiently inhibited the secretion of IL-17A-induced proinflammatory cytokines. Therefore, this lead anti-IL-17A mAb might be used as a potential best-in-class candidate for treating IL-17A related diseases.

10.
Article in Chinese | WPRIM | ID: wpr-703371

ABSTRACT

Objective To purify marmoset serum IgG, prepare and identify the antiserum and the rabbit anti-marmoset antibody IgG-HRP (horseradish peroxidase). Methods Using SDS-PAGE analysis to identify the serum IgG from HiTrapTM Protein G. The antiserum titer was determined by double immunodiffusion assay. The rabbit anti-marmoset IgG was labeled with HRP by improved sodium periodate method. ELISA and western blotting were used to evaluate the concentration and specificity of rabbit anti-marmoset IgG-HRP. Results The purity of purified marmoset serum IgG determined by SDS-PAGE was higher than 95% , and the anti-serum titer of the anti-marmoset IgG polyclonal antibody was 1∶64. The concentration of rabbit anti-marmoset IgG-HRP identified by direct ELISA was 1∶256 000, and that by western-blotting was 1∶15 000, with a strong specificity. Conclusions The IgG-HRP marker antibody is prepared and the specificity and concentration are identified by ELISA and western blotting. It reserves the resources for the detection system of marmoset pathogens and the molecular immunological testing system.

11.
Indian J Exp Biol ; 2017 Jan; 55(1): 21-26
Article in English | IMSEAR | ID: sea-181709

ABSTRACT

Tinospora cordifolia (Guduchi) is a widely used herb in Ayurvedic system of medicine known to possess immunomodulatory properties. The present study was aimed to study the activation of macrophages after in vitro guduchi treatment. The aqueous extract of T. cordifolia was found to enhance phagocytosis and pinocytosis in vitro. The rate of pinocytosis by macrophages when measured by uptake of horseradish peroxidase was significantly increased after guduchi treatment as compared to medium alone. The macrophages demonstrated an increased phagocytosis to non-infective microorganisms (heat killed yeast) and live infective microorganisms (E. coli) after guduchi treatment. The results demonstrate that Guduchi enhances macrophage activation as analyzed by cytochemical parameters.

12.
Acta Pharmaceutica Sinica B ; (6): 80-90, 2017.
Article in English | WPRIM | ID: wpr-256776

ABSTRACT

Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers. Traditional chemotherapy for this disease leads to serious side effects. Here we prepared an inhalable oridonin-loaded poly(lactic--glycolic)acid (PLGA) large porous microparticle (LPMP) fortreatment of NSCLC with the emulsion/solvent evaporation/freeze-drying method. The LPMPs were smooth spheres with many internal pores. Despite a geometric diameter of ~10 µm, the aerodynamic diameter of the spheres was only 2.72 µm, leading to highly efficient lung deposition.studies showed that most of oridonin was released after 1 h, whereas the alveolar macrophage uptake of LPMPs occurred after 8 h, so that most of oridonin would enter the surroundings without undergoing phagocytosis. Rat primary NSCLC models were built and administered with saline, oridonin powder, gemcitabine, and oridonin-loaded LPMPsairway, respectively. The LPMPs showed strong anticancer effects. Oridonin showed strong angiogenesis inhibition and apoptosis. Relevant mechanisms are thought to include oridonin-induced mitochondrial dysfunction accompanied by low mitochondrial membrane potentials, downregulation of BCL-2 expressions, upregulation of expressions of BAX, caspase-3 and caspase-9. The oridonin-loaded PLGA LPMPs showed high anti-NSCLC effects after pulmonary delivery. In conclusion, LPMPs are promising dry powder inhalations fortreatment of lung cancer.

13.
Article in Chinese | WPRIM | ID: wpr-495742

ABSTRACT

Objective To analyze the polymorphism of histidine rich protein 2(HRP II)gene in Plasmodium falciparum (Pfhrp2)from falciparum malaria patients in Yunnan Province,so as to lay the foundation for studying the defection of antigen genes of Plasmodium. Methods The filter paper blood samples and related information of falciparum malaria cases reported were obtained in Yunnan Province from August 2012 to September 2015. Under the guidance of the specific primers,the exon2 regions in Pfhrp2 gene in P. falciparum from DNA samples were amplified by PCR,and the PCR products were sequenced. The sequences of exon2 region in Pfhrp2 gene were blasted by comparing with the reference sequences AY816237,AY816240,and AY816301. Next,the polymorphism of the sequence in exon2 region of Pfhrp2 gene was analyzed by MEGA 5.04 software. The conserved sites and genetic distances between sequences were calculated by using the software as well,and the clustering tree was drawn according to the genetic distances between the amino acid sequences. Results A total of 218 bloods samples from the falciparum malaria cases in 15 prefectures of Yunnan Province were collected,and the sources of infection included Yun?nan,Africa and Myanmar. The PCR results showed that the exon2 regions in Pfhrp2 genes of 155 samples were positive by am?plification and their products were sequenced successfully. The sequence analysis showed that the length range of the amino acid residues of exon2 region in Pfhrp2 gene was from 115 aa to 298 aa,the average length was 239.7 aa. There was no statistically significance among the means of the amino acid residues of the isolates from Africa( 239.9 aa),Myanmar(239.5 aa)and Yun?nan(241.6 aa)(F=0.025,P>0.05). All the 155 amino acid sequences ended with type 12 repeat,98.1%(152/155)of them started with type 1 repeat and 1.9%(3/155)of them started with type 2. Type 2 presented most frequently repeat in all the se?quences and the average repeat times were 12.9. The homologous locus of the DNA sequences in exon2 regions of the 155 Pfhrp2 genes was 894 bp,among which the conservative sites accounted for 20.6%(186/894),and the variable sites for 78.2%(699/894). The genetic distances between the sequences of Africa isolates ranged from 0 to 0.741,and those of the Myanmar and Yun?nan isolates were 0-0.948 and 0-0.750,respectively. The cluster analysis showed that all the 155 sequences clustered into 3 cat?egories on genetic distances between amino acid sequences according to the size of the amino acid sequence length. At the same level,the sequences had approximate lengths and amino acid repeat types. Conclusion The sequence of exon2 region in Pfhrp2 gene of P. falciparum from falciparum malaria cases in Yunnan Province is highly polymorphic,the P. falciparum iso?lates are clustered mainly according to the size of the amino acid sequence of exon2 region in Pfhrp2 gene.

14.
Acta Pharmaceutica Sinica B ; (6): 475-491, 2016.
Article in English | WPRIM | ID: wpr-256804

ABSTRACT

Intestine is responsible for the biotransformation of many orally-exposed chemicals. The constitutive androstane receptor (CAR/Nr1i3) is known to up-regulate many genes encoding drug-metabolizing enzymes and transporters (drug-processing genes/DPGs) in liver, but less is known regarding its effect in intestine. Sixty-day-old wild-type andmice were administered the CAR-ligand TCPOBOP or vehicle once daily for 4 days. In wild-type mice,mRNA was down-regulated by TCPOBOP in liver and duodenum.mice had altered basal intestinal expression of many DPGs in a section-specific manner. Consistent with the liver data (Aleksunes and Klaassen, 2012), TCPOBOP up-regulated many DPGs (, and) in specific sections of small intestine in a CAR-dependent manner. However, the mRNAs ofandwere previously known to be up-regulated by TCPOBOP in liver but were not altered in intestine. Interestingly, many known CAR-target genes were highest expressed in colon where CAR is minimally expressed, suggesting that additional regulators are involved in regulating their expression. In conclusion, CAR regulates the basal expression of many DPGs in intestine, and although many hepatic CAR-targeted DPGs wereCAR-targets in intestine, pharmacological activation of CAR in liver and intestine are not identical.

15.
Acta Pharmaceutica Sinica B ; (6): 205-211, 2016.
Article in English | WPRIM | ID: wpr-309966

ABSTRACT

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a severe, life-threatening medical condition characterized by widespread inflammation in the lungs, and is a significant source of morbidity and mortality in the patient population. New therapies for the treatment of ALI are desperately needed. In the present study, we examined the effect of andrographolide sulfonate, a water-soluble form of andrographolide (trade name: Xi-Yan-Ping Injection), on lipopolysaccharide (LPS)-induced ALI and inflammation. Andrographolide sulfonate was administered by intraperitoneal injection to mice with LPS-induced ALI. LPS-induced airway inflammatory cell recruitment and lung histological alterations were significantly ameliorated by andrographolide sulfonate. Protein levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and serum were reduced by andrographolide sulfonate administration. mRNA levels of pro-inflammatory cytokines in lung tissue were also suppressed. Moreover, andrographolide sulfonate markedly suppressed the activation of mitogen-activated protein kinase (MAPK) as well as p65 subunit of nuclear factor-κB (NF-κB). In summary, these results suggest that andrographolide sulfonate ameliorated LPS-induced ALI in mice by inhibiting NF-κB and MAPK-mediated inflammatory responses. Our study shows that water-soluble andrographolide sulfonate may represent a new therapeutic approach for treating inflammatory lung disorders.

16.
Acta Pharmaceutica Sinica B ; (6): 316-322, 2015.
Article in English | WPRIM | ID: wpr-310021

ABSTRACT

Traditionally, determination of inhibitory potency of complement inhibitors is performed by the hemolytic assay. However, this assay is not applicable to the lectin pathway, thus impeding the understanding of complement inhibitors against the overall function of the complement system. The main objective of our study was to develop a specific enzyme-linked immunosorbent assay (ELISA) as an alternative method to assess the anti-complement activity, particularly against the lectin pathway. By using respective coating substrates against different activation pathways, followed by capturing the stable C3c fragments, our ELISA method can be used to screen complement inhibitors against the classical pathway and the lectin pathway. The inhibitory effect of suramin on the classical pathway, as measured by our hemolytic assay is consistent with previous reports. Further assessment of suramin and Bupleurum polysaccharides against the lectin pathway showed a good reproducibility of the method. Comparison of the lectin pathway IC50 between Bupleurum smithii var. parvifolium polysaccharides (1.055 mg/mL) and Bupleurum chinense polysaccharides (0.98 mg/mL) showed that, similar to the classical and alterative pathway, these two Bupleurum polysaccharides had comparable anti-complementary properties against the lectin pathway. The results demonstrate that the described ELISA assay can compensate for the shortcomings of the hemolytic assay in lectin pathway.

17.
Acta Pharmaceutica Sinica B ; (6): 554-563, 2015.
Article in English | WPRIM | ID: wpr-309996

ABSTRACT

The effects of tanshinone IIA on the proliferation of the human non-small cell lung cancer cell line A549 and its possible mechanism on the VEGF/VEGFR signal pathway were investigated. The exploration of the interaction between tanshinone IIA and its target proteins provides a feasible platform for studying the anticancer mechanism of active components of herbs. The CCK-8 assay was used to evaluate the proliferative activity of A549 cells treated with tanshinone IIA (2.5-80 μmol/L) for 24, 48 and 72 h, respectively. Flow cytometry was used for the detection of cell apoptosis and cell cycle perturbation. VEGF and VEGFR2 expression were studied by Western blotting. The binding mode of tanshinone IIA within the crystal structure of the VEGFR2 protein was evaluated with molecular docking analysis by use of the CDOCKER algorithm in Discovery Studio 2.1. The CCK-8 results showed that tanshinone IIA can significantly inhibit A549 cell proliferation in a dose- and time-dependent manner. Flow cytometry results showed that the apoptosis rate of tested group was higher than the vehicle control, and tanshinone IIA-treated cells accumulated at the S phase, which was higher than the vehicle control. Furthermore, the expression of VEGF and VEGFR2 was decreased in Western blot. Finally, molecular docking analysis revealed that tanshinone IIA could be stably docked into the kinase domain of VEGFR2 protein with its unique modes to form H-bonds with Cys917 and π-π stacking interactions with Val848. In conclusion, tanshinone IIA may suppress A549 proliferation, induce apoptosis and cell cycle arrest at the S phase. This drug may suppress angiogenesis by targeting the protein kinase domains of VEGF/VEGFR2.

18.
Article in English | IMSEAR | ID: sea-153482

ABSTRACT

Aim: The aim of this study was to determine the prevalence and density of malaria parasites in asymptomatic school children in Mutengene and evaluate the performance characteristics of the ‘CareStartTM Malaria HRP2 pf (CAT NO: G0141, ACCESSBIO)’ rapid diagnostic test (RDT) using light microscopy as a gold standard. Study Design: The study was a cross-sectional survey. Place and Duration of Study: The study was carried out in Mutengene, from February to March, 2013. Methodology: A total of 406 pupils were studied. Demographic data was taken for each child and capillary blood was collected. Blood films were prepared for the assessment of parasite density and speciation. A drop of blood was used on the RDT to determine the malaria status. Results: The mean age at 95% confidence interval (CI) was 8 ± 2 years (range = 4 -15 years) and the overall prevalence of malaria was 39.9% (162) by microscopy. The geometric mean parasite density (GMPD) was 2332.7 parasites/µL (range: 218 - 16000). Only 386 pupils were examined by both methods. More pupils were positive by microscopy (40.9%, CI = 36.1 - 45.9) than by RDT (27.9%, CI = 23.7 - 32.7) and the difference was statistically significant (χ2 = 16.1, P <0.0001). The majority of those detected had high infection (≥ 5000 parasite/µL). Less than 50% of those with low (25.0%, CI = 12.0 - 44.9), moderate (40.7%, CI = 32.24-49.70) and high parasitaemia (75%, CI = 5.00-89.82) were positive by RDT and the difference was significant (χ2 = 10.09, P = 0.006). The RDT showed a low sensitivity of 48.5% (CI = 40.3 – 56.9%) and specificity of 84.0% (CI = 80.0- 88.2%). Conclusion: More research needs to be done on the RDT to improve on its performance characteristics before it could be used in mass surveillance programmes.

19.
West Indian med. j ; 62(6): 497-503, July 2013. ilus, graf, tab
Article in English | LILACS | ID: biblio-1045686

ABSTRACT

This study was designed to determine qualitatively, the source of gastric vagal nerve fibres in the Agouti. A total of 18 male and female adult agoutis were used for the present investigation. Following anaesthesia, laparotomy was performed and the stomach exteriorized. Multiple intramuscular injections of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) were then made into different areas of the stomach in the experimental animals. The control animals were divided into four groups of two animals each. The first group had intraperitoneal injection of the tracer, the second had intramuscular injection of normal saline, the third group had injection of tracer into the hepatic portal vein and the last group had injection of the tracer into the gastric walls followed immediately by bilateral vagotomy. Following a survival period offive to seven days, the animals were sacrificed by transcardial perfusion, first with normal saline followed by fixative and finally with 20% buffered sucrose. Following perfusion, the brainstem was extracted from the brain, immersed in 20% buffered sucrose and kept refrigerated overnight for cryoprotection. The brainstems were subsequently sectioned serially, processed for WGA-HRP neurohistochemistry and then analysed under light and dark-field illuminations. The analysis of the sections taken from the experimental animals revealed bilateral presence of WGA-HRP labelled neurons in the dorsal motor nucleus of the vagus nerve (DMNV) and the nucleus ambiguus (nA) of the medulla oblongata. No labelled neurons were seen in any of the sections taken from the control animals. The implications of the findings are discussed.


Este estudio fue diseñado para determinar cualitativamente el origen de las fibras gástricas del nervio vago en el agutí. Un total de 18 agutíes adultos masculinos y femeninos fueron utilizados para la presente investigación. Después de la anestesia, se realizó una laparotomía y se sacó el estómago al exterior. Luego se hicieron múltiples inyecciones intramusculares de aglutinina de germen de trigo con peroxidasa de rábano (WGA-HRP) en diferentes áreas del estómago de los animales experimentales. Los animales del control fueron divididos en cuatro grupos de dos animales cada uno. Al primer grupo se le puso una inyección intraperitoneal del marcador; al segundo se le administró una inyección intramuscular de solución salina normal; al tercer grupo se le inyectó el marcador en la vena porta hepática; y al último grupo se le puso la inyección del marcador en las paredes gástricas, seguida inmediatamente por una vagotomía bilateral. Tras un periodo de supervivencia de cinco a siete días, los animales fueron sacrificados por perfusión transcardíaca, primero con solución salina normal, seguida de fijador, y finalmente con sacarosa tamponada al 20%. Después de la perfusión, el tronco encefálico fue extraído del cerebro, inmerso en sacarosa tamponada al 20%, y mantenido en refrigeración durante la noche para su crioprotección. Los tronos encefálicos fueron luego seccionados en serie, procesados para para el análisis neuro-histoquímico mediante aglutinina de germen de trigo con peroxidasa de rábano, y analizados entonces bajo iluminaciones de campo de luz y campo oscuro. El análisis de las secciones tomadas de animales experimentales reveló la presencia bilateral de neuronas etiquetadas WGA-HRP en el núcleo motor dorsal del nervio vago (DMNV) y en el núcleo ambiguo (nA) de la médula oblonga. No se observaron neuronas etiquetadas en ninguna de las secciones tomadas de los animales de control. Se discuten las implicaciones de los hallazgos.


Subject(s)
Animals , Male , Female , Autonomic Fibers, Preganglionic , Stomach/cytology , Vagus Nerve/anatomy & histology , Brain Stem/anatomy & histology , Neurons, Efferent/cytology , Rodentia
20.
Article in English | WPRIM | ID: wpr-320359

ABSTRACT

<p><b>OBJECTIVE</b>To study the effect of electromagnetic pulse (EMP) exposure on permeability of in vitro blood-brain-barrier (BBB) model.</p><p><b>METHODS</b>An in vitro BBB model, established by co-culturing brain microvascular endothelial cells (BMVEC) and astroglial cells (AC) isolated from rat brain, was exposed to EMP at 100 kV/m and 400 kV/m, respectively. Permeability of the model was assayed by measuring the transendothelial electrical resistance (TEER) and the horseradish peroxidase (HRP) transmission at different time points. Levels of BBB tight junction-related proteins were measured at 0, 1, 2, 4, 8, 12, 16, 20, 24 h after EMP exposure by Western blotting.</p><p><b>RESULTS</b>The TEER level was lower in BBB model group than in control group at 12 h after EMP, exposure which returned to its normal level at 24 h. The 24 h recovery process was triphasic and biphasic respectively after EMP exposure at 100 kV/m and 400 kV/m. Following exposure to 400 kV/m EMP, the HRP permeability increased at 1-12 h and returned to its normal level at 24 h. Western blotting showed that the claudin-5 and ZO-1 protein levels were changed after EMP exposure.</p><p><b>CONCLUSION</b>EMP exposure at 100 kV/m and 400 kV/m can increase the permeability of in vitro BBB model and BBB tight junction-related proteins such as ZO-1 and claudin-5 may change EMP-induced BBB permeability.</p>


Subject(s)
Animals , Blood-Brain Barrier , Radiation Effects , Capillary Permeability , Radiation Effects , Cells, Cultured , Electromagnetic Fields , Female , Rats , Rats, Sprague-Dawley
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