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Adenosine 5'triphosphate transport and accumulation during the cold preservation of rat hepatocytes in University of Wisconsin solution

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World Journal of Gastroenterology 2005年第13期11卷 1957-1964页

作者： María E.Mamprin Félix Vega Joaquín V.Rodriguez farmacología

AIM: We used isolated hepatocytes to investigate how different concentrations of ATP in the University of Wisconsin (UW) solution affected both cellular ATP content and cell viability during the cold storage and the rewarming step. The mechanism involved in ATP transport and accumulation in hypothermia was also ***: The cells were preserved up to 72 h in different conditions: UW solution without ATP (a-group),UW+5 mmol/L ATP (b-group), and UW+10 mmol/L ATP (c-group). The ATP content and the cell viability (LDH release) were determined during the cold storage and the rewarming step. In the groups a and c, the respiratory function of the cells at rewarming was studied. In addition,the cell volume of hepatocytes and the mechanism involved in ATP transport and accumulation were assessed. The extracellular degradation of exogenous nucleotides during transport experiments was investigated by a HPLC ***: After three days of cold storage a loss of cellular ATP content was observed in hepatocytes preserved either without nucleotides (a-group) or with 5 mmol/L ATP (b-group). In contrast, 10 mmol/L ATP (c-group) was able to maintain a normal ATP cellular content, with only a 6% diminution after 72 h of cold storage. The respiratory function was significantly different in hepatocytes preserved with 10 mmol/L ATP than without ATP. No significant change was detected for the three groups in cellular volume during the cold storage. We also report that the time course accumulation of [3H]-ATP by cold stored hepatocytes is a rapid process that is completed after 180 s with linear dependence on the extracellular ATP concentration (linear fitting results in a slope of 0.5624±0.1179 mmol/L ATP intracell/mmol/L ATP extracell).CONCLUSION: Our results show that, during hypothermic storage in UW solution, hepatocytes are permeable to ATP by a diffusive mechanism. Also, we found that it is ATP the main extracellular nucleotide available for transport and it is no

关键词： 5'三磷酸腺苷低温保存小鼠肝细胞扩散机制

Noise-induced hippocampal damage:potential mechanisms

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Neural Regeneration Research 2022年第3期17卷 563-564页

作者： Sonia Jazmín Molina Laura Ruth Guelman Universidad de Buenos Aires Consejo Nacional de Investigaciones Científicas y TécnicasCentro de Estudios Farmacológicos y Botánicos(CEFyBOUBA-CONICET)Facultad de MedicinaBuenos AiresArgentina Universidad de Buenos Aires Facultad de Medicina1^(a) Cátedra de FarmacologíaBuenos AiresArgentina

Exposure to noise of high intensities(> 80 dB) is considered a stressful event and might produce both auditory and extra-auditory damage,including different central nervous system(CNS) *** the CNS,the hippocampus(HC),a structure related to several cognitive functions,has shown to be particularly susceptible to the effects of noise.

关键词： damage auditory injuries

离体人类脐静脉中的缓激肽B1受体:体外调控过程的实验模型（英文）

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Acta Pharmacologica Sinica 2000年第2期 11-16页

作者： Sergio Pablo SARDI,Andrea Emilse ERRASTI,Verónica REY-ARES,María Pía ROGINES-VELO,Rodolfo Pedro ROTHLIN Departamento de farmacología Facultad de Medici-na Universidad de Buenos Aires Paraguay 2155 Piso 15 1121 Buenos Aires Argentina Departamento de farmacología Facultad de Medici-na Universidad de Buenos Aires Paraguay 2155 Piso 15 1121 Buenos Aires Argentina Departamento de farmacología Facultad de Medici-na Universidad de Buenos Aires Paraguay 2155 Piso 15 1121 Buenos Aires Argentina Departamento de farmacología Facultad de Medici-na Universidad de Buenos Aires Paraguay 2155 Piso 15 1121 Buenos Aires Argentina Departamento de farmacología Facultad de Medici-na Universidad de Buenos Aires Paraguay 2155 Piso 15 1121 Buenos Aires Argentina

Bradykinin (BK) B1 receptors are not normally expressed in physiological conditions but could be induced in immunopathological states. Molecular approaches have confirmed that BK B1 receptor gene is transcription-ally induced in injured tissues. In these situations, the cytokine network and other proinflammatory mediators are close linked to BK B1 receptor *** this article, we describe the functional characterization of the BK B1 receptor up-regulation process in the isolated human umbilical vein and the pharmacological tools employed to demonstrate the de novo synthesis of these receptors. BK B1 receptors are up-regulated in a time- and protein synthesis-dependent process. Furthermore, in this tissue we have demonstrated the close link between the BK B1 receptor sensitization and proinflammatory cytokines, such as interleukin-1 beta and tumor necrosis factor-alpha. We also discuss the possible relationship between nuclear factor-kappa B and BK B1 receptor induction in human umbilical vein.

关键词：缓激肽脐静脉上调(生理学) NF-κB

Medical plant extracts and natural compounds with a hepatoprotective effect against damage caused by antitubercular drugs: A review

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Asian Pacific Journal of Tropical Medicine 2016年第12期9卷 1116-1125页

作者： María Adelina Jiménez-Arellanes Gabriel Alfonso Gutiérrez-Rebolledo Mariana Meckes-Fischer Rosalba León-Díaz Unidad de Investigación Médica en farmacología.UMAE Hospital de Especialidades Centro Médico Nacional-Siglo XXI.Instituto Mexicano del Seguro Social

Drug-induced liver injury encompasses a spectrum of diseases ranging from mild biochemical abnormalities to acute liver failure; example of this scenery is hepatotoxicity caused by the first-line antituberculous drugs isoniazid, rifampin and pyrazinamide, which are basic for treatment of drug-sensible and drug-resistant tuberculosis. In the search for pharmacological alternatives to prevent liver damage, antitubercular drugs have been the subject of numerous studies and published reviews, a great majority of them carried out by Asian countries. At the same time, hepatoprotectors from plant source are now emerging as a possible alternative to counteract the toxic effects of these therapeutic agents. The present review aims to highlight the most recent studies on the subject, based information published in scientific databases such as Scopus and Pub Med.

关键词： Medicinal plants Hepatoprotective effect Antitubercular drugs-induced hepatotoxicity Natural compounds

Growth,phenology and N-utilization by invasive populations of Gunnera tinctoria

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Journal of Plant Ecology 2020年第5期13卷 589-600页

作者： Maurício Cruz Mantoani Alberto Benavent González Leopoldo García Sancho Bruce Arthur Osborne UCD School of Biology and Environmental Science and UCD Earth Institute University College DublinBelfieldDublin 4Ireland Departamento de farmacología Farmacognosia y BotánicaFacultad de FarmaciaUniversidad Complutense de Madrid28040 MadridSpain

智利大叶草(Gunnera tinctoria)是一种不同寻常的固氮植物,已入侵到了世界各地,通常入侵到低蒸发需求和/或高降雨的环境。在许多可以解释其作为一个成功的引入物种的机制中,差异性的物候特征可能起重要作用,但这可能取决于在次优化条件... 详细信息

智利大叶草(Gunnera tinctoria)是一种不同寻常的固氮植物,已入侵到了世界各地,通常入侵到低蒸发需求和/或高降雨的环境。在许多可以解释其作为一个成功的引入物种的机制中,差异性的物候特征可能起重要作用,但这可能取决于在次优化条件下生长和利用营养物质的能力。我们研究了智利大叶草在物候和固氮能力方面是否具有优势,并将其与受智利大叶草入侵影响最大的本地物种灯芯草(Juncus effusus)进行了比较。2016-2017年,我们每周或每两周对爱尔兰阿奇尔岛的长期种群进行物候学评估。在测量土壤温度,湿度和氧化还原电位的同时,收集了叶和花序数,叶总面积,光截获和地上生物量的数据。利用δ15N同位素并结合原位乙炔还原测量的方法评估了用于支持季节生长的固氮能力的重要性。研究结果表明,2016-2017年,智利大叶草和灯芯草开始生长的时间不同,智利大叶草叶片出现和展叶的时间较早,水分利用率较高时地上生物量最大。智利大叶草的早期生长依赖于预先形成的结构,5月下旬冠层发育达到最大,并且早于灯芯草。虽然在3月份观察到固氮作用,但这对冠层发育后期的生长有更显著的贡献。基于δ15N同位素分析结果表明,早期生长主要与根状茎的氮转移有关,而幼苗主要依赖于固氮作用。这一发现强调了养分调动对早期生长的重要性,并表明固氮能力的重要性可能在不同的发育过程中有所不同,并且其在入侵过程的不同阶段也是如此。

关键词：生长入侵物种智利大叶草(Gunnera tinctoria) 灯芯草(Juncus effusus) 固氮

Altered blood-brain barrier permeability in rats with prehepatic portal hypertension turns to normal when portal pressure is lowered

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World Journal of Gastroenterology 2006年第9期12卷 1367-1372页

作者： Francisco Eizayaga Camila Scorticati Juan P Prestifilippo Salvador Romay Maria A Fernandez José L Castro Abraham Lemberg Juan C Perazzo Laboratory of Portal Hypertension Department of Pathophysiology School of Pharmacy and BiochemistryUniversity of Buenos AiresBuenos AiresArgentina Catedra de farmacología School of Pharmacy and Biochemistry University of Buenos Aires Buenos Aires Argentina Laboratory of Portal Hypertension Department of Pathophysiology School of Pharmacy and Biochemistry University of Buenos Aires Buenos AiresArgentina

AIM: To study the blood-brain barrier integrity in prehe-patic portal hypertensive rats induced by partial portal vein ligation, at 14 and 40 d after ligation when portal pressure is spontaneously normalized. METHODS: Adult male Wistar rats were divided into four groups: GroupⅠ: Sham14d, sham operated; GroupⅡ: PH14d, portal vein stenosis; (both groups were used 14 days after surgery); GroupⅢ: Sham40d, Sham operated and GroupⅣ: PH40d Portal vein stenosis (GroupsⅡandⅣused 40 d after surgery). Plasma ammonia, plasma and cerebrospinal fluid protein and liver enzymes concentrations were determined. Trypan and Evans blue dyes, systemically injected, were investigated in hippocampus to study blood-brain barrier integrity. Portal pressure was periodically recorded. RESULTS: Forty days after stricture, portal pressure was normalized, plasma ammonia was moderately high, and both dyes were absent in central nervous system parenchyma. All other parameters were reestablished. When portal pressure was normalized and ammonia level was lowered, but not normal, the altered integrity of blood-brain barrier becomes reestablished. CONCLUSION: The impairment of blood-brain barrier and subsequent normalization could be a mechanism involved in hepatic encephalopathy reversibility, Hemo-dynamic changes and ammonia could trigger blood-brain barrier alterations and its reestablishment.

关键词：血脑屏障门静脉高压治疗病理机制

Current and novel approaches in the pharmacological treatment of hepatocellular carcinoma

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World Journal of Gastroenterology 2023年第17期29卷 2571-2599页

作者： Fernanda Villarruel-Melquiades María Eugenia Mendoza-Garrido Claudia M García-Cuellar Yesennia Sánchez-Pérez Julio Isael Pérez-Carreón Javier Camacho Departamento de farmacología Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional(CINVESTAV-IPN)Mexico City 07360Mexico Departamento de Fisiología Biofísica y NeurocienciasCentro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional(CINVESTAVIPN)Mexico City 07360Mexico Subdirección de Investigación Básica Instituto Nacional de Cancerología(INCan)Mexico City 14080Mexico Instituto Nacional de Medicina Genómica Instituto Nacional de Medicina Genómica(INMEGEN)Mexico City 14610Mexico

Hepatocellular carcinoma(HCC)is one of the most lethal malignant tumours *** mortality-to-incidence ratio is up to 91.6%in many countries,representing the third leading cause of cancer-related *** drugs,including the multikinase inhibitors sorafenib and lenvatinib,are first-line drugs used in HCC ***,these therapies are ineffective in most cases due to late diagnosis and the development of tumour ***,novel pharmacological alternatives are urgently *** instance,immune checkpoint inhibitors have provided new approaches targeting cells of the immune ***,monoclonal antibodies against programmed cell death-1 have shown benefits in HCC *** addition,drug combinations,including first-line treatment and immunotherapy,as well as drug repurposing,are promising novel therapeutic ***,we review the current and novel pharmacological approaches to fight *** studies,as well as approved and ongoing clinical trials for liver cancer treatment,are *** pharmacological opportunities analysed here should lead to significant improvement in HCC therapy.

关键词： Liver cancer Systemic therapy Immunotherapy Drug repurposing Drug combinations Hepatocellular carcinoma

Natural compounds and extracts from Mexican medicinal plants with anti-leishmaniasis activity: An update

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Asian Pacific Journal of Tropical Medicine 2017年第12期10卷 1105-1110页

作者： Gabriel Alfonso Gutiérrez-Rebolledo Susan Drier-Jonas María Adelina Jiménez-Arellanes Unidad de Investigación Médica en farmacología Hospital de EspecialidadesCentro Médico Nacional Siglo XXIInstituto Mexicano del Seguro SocialAv. Cuauhtémoc 330Col. DoctoresDelg. Cuauhtémoc06720 Ciudad de MéxicoMexico

Leishmaniasis is considered as an emerging, uncontrolled disease and is endemic in 98 countries. Annually, about 2 million cases of cutaneous and 500000 cases of visceraltype leishmaniasis are recorded and 60000 persons died from the disease. In Mexico,cutaneous leishmaniasis is known as chiclero's ulcer and is reported in 22 states, it is considered as a health problem. For its treatment, pentavalent antimonial drugs are administered. These drugs cause severe side effects, are costly. Drug-resistant cases have been reported and have been developing for over 70 years. One alternative to the drugs that are currently available is to find active molecules in medicinal plants. Dihydrocorynantheine, corynantheine and corynantheidine are active against Leishmania major,while harmane, pleiocarpin, buchtienin, luteolin and quercetin are active against Leishmania donovani. In Mexico, about 20 medicinal plants have been evaluated against Leishmania mexicana, among which the most active are Tridax procumbens, Lonchocarpus xuul and Pentalinon andrieuxii. From these plants, active compounds with IC_(50)≤30 mg/mL or m M have been isolated, such as 3(S)-16,17-didehydrofalcarinol or Oxylipin, cholestra-4,20,24-trien-3-one or pentalinosterol, 24-methylcholest-4-24(28)-dien-3-one, cholest-4-en-3-one, 6,7-dihydroneridie-none, neridienone, cholest-5,20,24-trien-3β-ol, and isocordoin. Today, only pentalinonsterol has been synthesized and assayed in the visceral leishmaniasis experimental model using BALB/c mice infected with Leishmania donovani. Liposome formulation of this compound administered by intravenous route at 2.5 mg/kg showed a significant reduction of parasite load in mouse liver and spleen.

关键词： Active extracts Leishmaniasis Antileishmanicidal activity Natural compounds Mexican medicinal plants

Peripheral Analgesic and Anti-Inflammatory Effects of Smilax canariensis in an Animal Model

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Pharmacology & Pharmacy 2015年第8期6卷 391-400页

作者： Sandra Dévora Susana Abdala Domingo Martín-Herrera Unidad de farmacología y Farmacognosia Sección de Farmacia Universidad de La Laguna San Cristóbal de La Laguna Spain

Smilax canariensis Brouss. ex Willd. is an endemic plant of the Canary Islands. Its rhizomes, leaves and stems have been traditionally used in Canary folk medicine to treat a wide variety of conditions including pain. Our objective is to investigate the analgesic and anti-inflammatory activities of different extracts of S. canariensis in Swiss mice, using established biological models for pain and inflammation, such as phenylquinone writhing test, formalin test, tail-flick test and mouse paw edema induced by carrageenan. Oral administration of S. canariensis extracts significantly reduce writhing episodes evoked by phenylquinone injection in a dose-dependent manner;and higher doses result in a reduction of pain similar to or higher than that of the reference drug piroxicam (59.56%;p < 0.01). The extracts also cause a marked dose-dependent inhibition of for-malin-induced pain in the second phase but only minimal inhibition of tail-flick behavior, suggesting that S. canariensis is not a centrally acting analgesic. Finally, in the carrageenan-induced hind paw edema model, the extracts show a moderate anti-inflammatory effect, the most active being the ethyl acetate fraction at 200 mg/kg p.o. (33.33%;p < 0.05). Our results suggest that S. canariensis extracts have clear dose-dependent peripheral analgesic effects, which lends support to the traditional use of this medicinal plant to treat pain associated with inflammatory or other processes.

关键词： Smilax canariensis Smilacaceae Medicinal Plant Folk Medicine Analgesic Activity Anti-Inflammatory Activity