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1.
Article in Chinese | WPRIM | ID: wpr-828521

ABSTRACT

OBJECTIVE@#To study the plasma concentration and pharmacokinetics of 3, 29-Dibenzoyl Karounitriol (3, 29-DK) from sustained- release pellets and extracts of Trichosanthes at different time points in rats using high-performance liquid chromatography- tandem mass spectrometry (LC-MS/MS).@*METHODS@#Healthy male SD rats were given a single gavage of Trichosanthes sustained-release pellets or Trichosanthes extract, and orbital blood samples were taken at different time points within 48 h after drug administration in the pellet group and within 5 h in Trichosanthes extract group for determination of the plasma concentrations of 3, 29-DK using LC-MS/MS. The standard curve of 3, 29-DK content was established, and the specificity, minimum detection limit, precision and accuracy, extraction recovery, stability and matrix effect of LC-MS/MS analysis were assessed. The mean plasms levels of 3, 29-DK at different time points after the drug administration were determined and its pharmacokinetic parameters were calculated using Das 2.0 software.@*RESULTS@#LC-MS/MS analysis showed a good linearity of 3, 29-DK concentration within the range of 0.5-32 ng/mL, and the results of methodological validation confirmed the validity of this method for biological sample determination. Trichosanthes sustained-release pellets and Trichosanthes extract showed significant differences in their AUC, AUC, MRT, MRT, t and T of 3, 29-DK after administration in rats ( < 0.05).@*CONCLUSIONS@#Trichosanthes sustained-release pellets are capable of sustained-release of 3, 29-DK in rats, and thus provides a basis for the study of new dosage forms of Trichosanthes.


Subject(s)
Animals , Area Under Curve , Benzoates , Pharmacokinetics , Chromatography, Liquid , Delayed-Action Preparations , Male , Rats , Rats, Sprague-Dawley , Reproducibility of Results , Tandem Mass Spectrometry , Trichosanthes , Chemistry
2.
Braz. J. Vet. Res. Anim. Sci. (Online) ; 56(3): e155078, out. 2019.
Article in English | ID: biblio-1025169

ABSTRACT

The various studies on the manipulation of the estrous cycle culminated in the development of estrous and ovulation synchronization protocols, to the point of defining an optimum moment for artificial insemination. The induction of ovulation is a primordial part for the determination of the moment of the TAI, so to study which hormones and how they behave allows a better understanding of this physiological process and, to manipulate it efficiently. The aim of the present study was to compare the use of estradiol benzoate (EB) and cypionate (ECP) as ovulation inducer in Girolando cows submitted to Timed Artificial Insemination (TAI). Ovulations of 108 Girolando cows were synchronized and the initial day of treatment, recorded as D0, which was when the animals received an intravaginal device containing 1g of progestogen and an intramuscular application (im) of 2mg of EB. After 8 days (D8), the device was removed and 500µg of cloprostenol (im) was administered to all females. Then, the animals were randomly divided into two treatments: BG Group (n = 52) and CG Group (n = 56). The CG animals received 1mg of ECP (im) as the ovulation inducer at the time of device removal, while BG Group cows received 1mg of EB (im) 24 h later (D9). TAI occurred at D10. After device removal, ultrasound evaluations were performed every 12 h up to ovulation. The following reproductive parameters were evaluated: interval from intravaginal device removal to ovulation - IDO (hours); interval from ovulation to TAI-IOT (hours); diameter of the largest follicle at intravaginal device removal (mm); maximum diameter of the DF (mm) at D10; the dominant follicle growth rate (mm/day); synchronization rate - SR (%); ovulation rate - OR (%) and PR - pregnancy rate (%). Only the ovulation rate presented a statistical difference (p<0.05). In conclusion, despite the ovulation rate difference, both estradiol esters administered were effective and presented similar pregnancy rates in Girolando cows submitted to TAI.


Os diversos estudos sobre manipulação do ciclo estral culminaram com o desenvolvimento de protocolos de sincronização do estro e da ovulação, a ponto de se definir um momento ótimo para a inseminação artificial. A indução da ovulação é parte primordial para a determinação do momento da IATF. Dessa forma, estudar quais hormônios e como eles se comportam permite compreender melhor esse processo fisiológico e, ainda, manipulá-lo de forma eficiente. O objetivo do presente estudo foi comparar o uso de benzoato de estradiol (BE) e cipionato (ECP) em vacas Girolando submetidas à inseminação artificial em tempo fixo (IATF). As ovulações de 108 vacas Girolando foram sincronizadas e no início do tratamento, D0, os animais receberam um dispositivo intravaginal contendo 1g de progestágeno e uma aplicação intramuscular (im) de 2mg de BE. No D8, o dispositivo foi removido e 500µg de cloprostenol (im) foram administrados a todas as fêmeas. Depois disso, os animais foram divididos aleatoriamente em dois tratamentos: Grupo GB (n = 52) e Grupo GC (n = 56). Os animais do Grupo GC receberam 1mg de ECP (im) como indutor de ovulação no momento da retirada do dispositivo, enquanto as vacas do Grupo GB receberam 1mg de BE (im) 24 horas depois (D9). IATF ocorreu em D10. Após a remoção do dispositivo, as avaliações ultrassonográficas foram realizadas a cada 12 horas até a ovulação. Os parâmetros reprodutivos avaliados foram: intervalo entre a retirada do dispositivo intravaginal de P4 e a ovulação- IRD (horas); intervalo entre a ovulação e a IATF- IOI (horas); diâmetro do maior folículo na retirada do dispositivo intravaginal de P4 (mm); taxa de crescimento do FD-TCFD (mm/dia); taxa de sincronização - TS (%); taxa de ovulação- TO (%) e taxa de concepção - TC (%). Apenas a taxa de ovulação apresentou diferença estatística (p<0.05). Em conclusão, apesar da diferença na taxa de ovulação, ambos os ésteres de estradiol administrados foram eficazes e apresentaram taxas de prenhez semelhantes em vacas Girolando submetidas a IATF.


Subject(s)
Animals , Female , Pregnancy , Cattle , Benzoates/analysis , Cattle/embryology , Insemination, Artificial , Estradiol/analysis
3.
Rev. méd. Chile ; 146(9): 1074-1078, set. 2018. tab, graf
Article in Spanish | LILACS | ID: biblio-978800

ABSTRACT

We report a 51-year-old female who had a first episode of thrombocytopenia at 23 years of age during a pregnancy. At the age of fifty, a hysterectomy was indicated due to a metrorrhagia: a platelet count of 21,000/ul was detected. She was treated with eltrombopag with a good response. The family history of the patient revealed the presence of thrombocytopenia in several family members. Suspecting a hereditary thrombocytopenia, a genetic study revealed a mutation in the MYH-9 gene. This mutation can be suspected when there is a family history of thrombocytopenia with autosomal dominant inheritance, macrothrombocytopenia and in this particular case, due to the response to thrombopoietin receptor agonist, eltrombopag.


Subject(s)
Humans , Female , Middle Aged , Thrombocytopenia/congenital , Hearing Loss, Sensorineural/diagnosis , Hearing Loss, Sensorineural/genetics , Platelet Count , Pyrazoles , Thrombocytopenia/diagnosis , Thrombocytopenia/genetics , Benzoates , Biopsy , Genetic Diseases, Inborn , Hydrazines , Mutation
4.
West Indian med. j ; 67(2): 110-113, Apr.-June 2018. graf
Article in English | LILACS | ID: biblio-1045830

ABSTRACT

ABSTRACT Objective: To investigate the secondary metabolites from the cultures of Streptomyces sp CSDX076. Methods: The compounds were isolated using column chromatography and RP-18 medium-pressure liquid chromatography. Their structures were elucidated by one-dimensional and two-dimensional nuclear magnetic resonance spectroscopic methods in combination with mass spectrometry experiments. Results: Four compounds were isolated from the cultures of Streptomyces sp CSDX076 and identified as aurantiamide benzoate, deoxytryptoquivaline, 2-acetyl-3,5-dihydroxyl-benzene acetic acid, and 2-acetyl-3,5-dihydroxyl-benzene ester. Conclusion: It was the first time that the four isolated compounds were obtained from the Streptomyces genus.


RESUMEN Objetivo: Investigar los metabolitos secundarios de los cultivos de Streptomyces sp CSDX076. Métodos: Los compuestos fueron aislados usando la cromatografía de columna y cromatografía líquida RP-18 de presión media. Sus estructuras fueron dilucidadas mediante métodos espectroscópicos de resonancia magnética nuclear unidimensional y bidimensional, combinados con experimentos de espectrometría de masa. Resultados: Cuatro compuestos de culturas de Streptomyces sp CSDX076 fueron aislados e identificados como benzoato de aurantiamida, deoxitriptoquivalina, ácido acético 2-acetil-3,5-dihidroxil-benzeno, y éster 2-acetil-3,5-dihidroxil-benzeno. Conclusión: Fue la primera vez que los cuatro compuestos aislados se obtuvieron del género Streptomyces.


Subject(s)
Streptomyces/chemistry , Benzoates/isolation & purification , Mass Spectrometry , Magnetic Resonance Spectroscopy , Chromatography, Liquid
5.
Article in English | WPRIM | ID: wpr-716843

ABSTRACT

PURPOSE: To characterize the relationship between serum estradiol levels and the expression of glucose transporter type 4 (Glut4) in the pubococcygeus and iliococcygeus muscles in female rats. METHODS: The muscles were excised from virgin rats during the metestrus and proestrus stages of the estrous cycle, and from sham and ovariectomized rats implanted with empty or estradiol benzoate–filled capsules. The expression of estrogen receptors (ERs) was inspected in the muscles at metestrus and proestrus. Relative Glut4 expression, glycogen content, and serum glucose levels were measured. Appropriate statistical tests were done to identify significant differences (P≤0.05). RESULTS: The pubococcygeus and iliococcygeus muscles expressed ERα and ERβ. Glut4 expression and glycogen content in the pubococcygeus muscle were higher at proestrus than at metestrus. No significant changes were observed in the iliococcygeus muscle. In ovariectomized rats, the administration of estradiol benzoate increased Glut4 expression and glycogen content in the pubococcygeus muscle alone. CONCLUSIONS: High serum estradiol levels increased Glut4 expression and glycogen content in the pubococcygeus muscle, but not in the iliococcygeus muscle.


Subject(s)
Animals , Benzoates , Blood Glucose , Capsules , Estradiol , Estrous Cycle , Female , Glucose Transport Proteins, Facilitative , Glucose Transporter Type 4 , Glucose , Glycogen , Humans , Metabolism , Metestrus , Muscles , Ovariectomy , Pelvic Floor , Proestrus , Rats , Receptors, Estrogen
6.
An. bras. dermatol ; 92(5,supl.1): 59-61, 2017. tab, graf
Article in English | LILACS | ID: biblio-887080

ABSTRACT

Abstract Deferasirox is an iron chelator agent used in the treatment of diseases with iron overload, such as thalassemia and myelodysplastic syndrome. Although the majority of adverse reactions of deferasirox involve gastrointestinal symptoms and increase in serum creatinine and transaminases, skin rashes, such as maculopapular and urticarial eruptions, have also been reported. This study reports a case of myelodysplastic syndrome with urticarial vasculitis due to deferasirox therapy. Drug eruption was been confirmed by means of a challenge test, together with histopathological and clinical findings. To the best of our knowledge, we report the first case of deferasirox-induced urticarial vasculitis. Physicians should be aware of the possibility of urticarial vasculitis on deferasirox therapy and the fact that the discontinuation of the drug generally results in improvement.


Subject(s)
Humans , Female , Aged , Triazoles/adverse effects , Urticaria/chemically induced , Vasculitis/chemically induced , Benzoates/adverse effects , Myelodysplastic Syndromes/drug therapy , Iron Chelating Agents/adverse effects , Drug Eruptions/etiology , Urticaria/pathology , Vasculitis/pathology , Biopsy , Drug Eruptions/pathology
7.
Braz. j. med. biol. res ; 50(12): e6087, 2017. graf
Article in English | LILACS | ID: biblio-888963

ABSTRACT

Using an iron overload mouse model, we explored the protective effect of deferasirox (DFX) and N-acetyl-L-cysteine (NAC) on injured bone marrow hematopoietic stem/progenitor cells (HSPC) induced by iron overload. Mice were intraperitoneally injected with 25 mg iron dextran every 3 days for 4 weeks to establish an iron overload (Fe) model. DFX or NAC were co-administered with iron dextran in two groups of mice (Fe+DFX and Fe+NAC), and the function of HSPCs was then examined. Iron overload markedly decreased the number of murine HSPCs in bone marrow. Subsequent colony-forming cell assays showed that iron overload also decreased the colony forming capacity of HSPCs, the effect of which could be reversed by DFX and NAC. The bone marrow hematopoiesis damage caused by iron overload could be alleviated by DFX and NAC.


Subject(s)
Animals , Male , Acetylcysteine/pharmacology , Triazoles/pharmacology , Benzoates/pharmacology , Hematopoietic Stem Cells/drug effects , Iron Chelating Agents/pharmacology , Free Radical Scavengers/pharmacology , Iron Overload/prevention & control , Protective Agents/pharmacology , Reference Values , Time Factors , Reproducibility of Results , Treatment Outcome , Reactive Oxygen Species/analysis , Colony-Forming Units Assay , Disease Models, Animal , Flow Cytometry , Hematopoiesis/drug effects , Mice, Inbred C57BL
8.
Arq. bras. med. vet. zootec ; 68(5): 1159-1167, set.-out. 2016. tab, graf, ilus
Article in English | ID: biblio-827902

ABSTRACT

Two experiments were conducted aiming to evaluate the effects of two ovulatory inducers (Exp.1) and equine chorionic gonadotropin (eCG; Exp.2) on follicular and luteal dynamics in a fixed-time AI (FTAI) protocol in locally adapted Curraleiro Pé-Duro cows. In Exp. 1 multiparous cows (n=12) received an intravaginal device containing 1g of progesterone (P4) for 8 days and 2mg of estradiol benzoate (EB) intramuscularly (IM) at device insertion (Day 0). At device removal (Day 8) 0.150mg of Sodium D-Cloprostenol was administered IM and the cows were randomly assigned to receive 1mg of EB (EB8) or 1mg of estradiol cypionate (EC8) IM, or to not receive any ovulatory inducer (Control). All the animals participated in all treatments (crossover). The interval from P4 removal to ovulation was shorter and less variable in the EB8 treatment group (P≤0.05). In Exp. 2 (crossover), multiparous cows (n=12) received the same hormonal treatment as the EB8 group in Exp.1. At device removal (Day 8) cows were randomly assigned to receive 300UI of eCG IM or to not receive eCG (Control). No difference was ascertained on follicular and luteal parameters in Exp. 2 (P>0.05). We concluded that EB can be used as the ovulatory inducer (Exp. 1) in a FTAI protocol in Curraleiro Pé-Duro cows. However, eCG (Exp. 2) was not able to stimulate follicular and luteal development. This result is probably due to the adaptive capacity of Curraleiro Pé-Duro cows that maintained a satisfactory body condition score even in dry and hot environments.(AU)


Foram realizados dois experimentos com o objetivo de avaliar o efeito de dois indutores da ovulação e da gonadotrofina coriônica equina (eCG) na dinâmica folicular e luteal, em um protocolo de inseminação artificial em tempo fixo (IATF) em vacas localmente adaptadas da raça Curraleiro Pé-Duro. No experimento 1, vacas pluríparas receberam um dispositivo intravaginal contendo 1g de progesterona (P4) durante oito dias e 2mg de benzoato de estradiol (BE) intramuscular (IM) no momento da inserção do dispositivo (dia zero). Na retirada do dispositivo (dia oito), as vacas receberam 0,150mg de D-cloprostenol sódico IM e foram separadas aleatoriamente para receber 1mg de BE IM (BE8) ou 1mg de cipionato de estradiol IM (CE8), ou nenhum indutor da ovulação (controle). Todos os animais participaram de todos os tratamentos (crossover). O intervalo entre a retirada da P4 e a ovulação foi menor e menos variável no tratamento BE8 (P≤0,05). O momento da ovulação foi mais precoce e mais concentrado nos animais do grupo BE 8. No experimento 2 (crossover), vacas pluríparas receberam o mesmo tratamento hormonal do grupo BE8 do experimento1. Na retirada do dispositivo (dia 8), as vacas foram separadas aleatoriamente para receberem 300UI de eCG IM, enquanto o controle não. Não houve diferença nos parâmetros foliculares e luteais avaliados no experimento 2 (P>0,05). Em conclusão, o BE pode ser utilizado como indutor da ovulação (experimento 1) em protocolos de IATF em vacas Curraleiras Pé-Duro. Entretanto, o eCG (experimento 2) não foi capaz de estimular o desenvolvimento folicular e luteal. Esse resultado é devido provavelmente à capacidade adaptativa das vacas Curraleiras Pé-Duro em manter uma condição corporal satisfatória mesmo em condições de clima seco e quente.(AU)


Subject(s)
Animals , Female , Cattle , Gonadotropins, Equine , Insemination, Artificial/methods , Insemination, Artificial/veterinary , Ovulation Induction/methods , Benzoates/therapeutic use , Estradiol/therapeutic use
9.
Article in Chinese | WPRIM | ID: wpr-815063

ABSTRACT

OBJECTIVE@#To examine the expression of liver X receptor-β (LXR-β) in human gastric cancer tissue, and to explore the effect of GW3965, an agonist of LXRs, on proliferation of gastric cancer cell line SGC-7901.
@*METHODS@#The immunohistochemical assay was used to detect the expression of LXR-β, activating transcription factor 4 (ATF4) in gastric cancer tissues and the corresponding pericarcinoma tissues in 114 patients. Real-time quantitative PCR and Western blot were used to determine mRNA and protein levels of ATF4 and ATP-binding cassette 1 (ABCA1), one of the downstream target genes of LXRs, in SGC-7901 cells with or without GW3965 treatment. Cell counting kit-8 (CCK-8) assay was performed to detect cell proliferation. The expression of ATF4 was silenced by short hairpin RNA (shRNA).
@*RESULTS@#The expressions of LXR-β and ATF-4 were obviously down-regulated in the gastric cancer tissues than that in the corresponding pericarcinoma tissues (both P<0.05). Compared with the control cells, GW3965 treatment inhibited proliferation of SGC-7901 cells and up-regulated ATF4 and ABCA1 expressions (both P<0.05). Knockdown of ATF4 can reverse the antiproliferative effect of GW3965 on SGC-7901 cells.
@*CONCLUSION@#The expression of LXR-β is decreased in human gastric cancer tissues, and activation of LXRs by GW3965 could inhibit the proliferation of SGC-7901 cells via ATF4.


Subject(s)
Activating Transcription Factor 4 , Genetics , Metabolism , Benzoates , Pharmacology , Benzylamines , Pharmacology , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Neoplastic , Gene Silencing , Humans , Liver X Receptors , Orphan Nuclear Receptors , Genetics , Metabolism , RNA, Messenger , Genetics , Metabolism , RNA, Small Interfering , Genetics , Stomach Neoplasms , Pathology , Up-Regulation
10.
Article in English | WPRIM | ID: wpr-812633

ABSTRACT

The present study was designed to determine the intestinal bacterial metabolites of trollioside and isoquercetin and their antibacterial activities. A systematic in vitro biotransformation investigation on trollioside and isoquercetin, including metabolite identification, metabolic pathway deduction, and time course, was accomplished using a human intestinal bacterial model. The metabolites were analyzed and identified by HPLC and HPLC-MS. The antibacterial activities of trollioside, isoquercetin, and their metabolites were evaluated using the broth microdilution method with berberine as a positive control, and their potency was measured as minimal inhibitory concentration (MIC). Our results indicated that trollioside and isoquercetin were metabolized by human intestinal flora through O-deglycosylation, yielding aglycones proglobeflowery acid and quercetin, respectively The antibacterial activities of both metabolites were more potent than that of their parent compounds. In conclusion, trollioside and isoquercetin are totally and rapidly transformed by human intestinal bacteria in vitro and the transformation favors the improvement of the antibacterial activities of the parent compounds.


Subject(s)
Activation, Metabolic , Anti-Bacterial Agents , Metabolism , Bacteria , Metabolism , Benzoates , Metabolism , Biotransformation , Gastrointestinal Microbiome , Glucosides , Metabolism , Humans , Intestines , Microbiology , Microbial Sensitivity Tests , Models, Biological , Quercetin , Metabolism
11.
Article in English | WPRIM | ID: wpr-109562

ABSTRACT

BACKGROUND/AIMS: The treatment of chronic myeloid leukemia (CML) has achieved impressive success since the development of the Bcr-Abl tyrosine kinase inhibitor, imatinib mesylate. Nevertheless, resistance to imatinib has been observed, and a substantial number of patients need alternative treatment strategies. METHODS: We have evaluated the effects of deferasirox, an orally active iron chelator, and imatinib on K562 and KU812 human CML cell lines. Imatinib-resistant CML cell lines were created by exposing cells to gradually increasing concentrations of imatinib. RESULTS: Co-treatment of cells with deferasirox and imatinib induced a synergistic dose-dependent inhibition of proliferation of both CML cell lines. Cell cycle analysis showed an accumulation of cells in the subG1 phase. Western blot analysis of apoptotic proteins showed that co-treatment with deferasirox and imatinib induced an increased expression of apoptotic proteins. These tendencies were clearly identified in imatinib-resistant CML cell lines. The results also showed that co-treatment with deferasirox and imatinib reduced the expression of BcrAbl, phosphorylated Bcr-Abl, nuclear factor-kappaB (NF-kappaB) and beta-catenin. CONCLUSIONS: We observed synergistic effects of deferasirox and imatinib on both imatinib-resistant and imatinib-sensitive cell lines. These effects were due to induction of apoptosis and cell cycle arrest by down-regulated expression of NF-kappaB and beta-catenin levels. Based on these results, we suggest that a combination treatment of deferasirox and imatinib could be considered as an alternative treatment option for imatinib-resistant CML.


Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Apoptosis Regulatory Proteins/metabolism , Benzoates/pharmacology , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Resistance, Neoplasm/drug effects , G1 Phase Cell Cycle Checkpoints/drug effects , Humans , Imatinib Mesylate/pharmacology , Iron Chelating Agents/pharmacology , K562 Cells , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Protein Kinase Inhibitors/pharmacology , Signal Transduction/drug effects , Triazoles/pharmacology
12.
Chinese Medical Journal ; (24): 8-14, 2016.
Article in English | WPRIM | ID: wpr-310719

ABSTRACT

<p><b>BACKGROUND</b>G-protein β-polypeptide 3 (GNB3) is a β subunit isoform of G-protein that plays important role in signal transduction of membrane G-protein coupled receptors (GPCRs). The GNB3 splice variant C825T (rs5443) is associated with risk for essential hypertension (EH) and efficacy of therapeutic drugs targeting GPCRs. It is unknown whether the polymorphism is associated with blood pressure (BP) response to telmisartan or amlodipine, two widely prescribed antihypertensive drugs.</p><p><b>METHODS</b>A total of 93 subjects initially diagnosed as EH were recruited and underwent a 4-week treatment with telmisartan (42 patients) or amlodipine (51 patients) monotherapy. Both baseline and after-treatment BP were measured. GNB3 C825T polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism.</p><p><b>RESULTS</b>Baseline systolic BP (SBP) and diastolic BP (DBP) were comparable among C825T genotypes in both telmisartan and amlodipine treatment groups. Patients with the CT or TT genotypes showed significantly lower body mass index (BMI) as compared with CC homozygotes in both groups (P < 0.05, respectively). GNB3 825TT homozygotes showed significantly higher after-treatment DBP and mean arterial pressure (MAP) than those carrying at least one 825C allele (P < 0.01) in the telmisartan treatment group. No difference in after-treatment SBP, DBP, and MAP levels among C825T genotypes was observed in the amlodipine treatment group. No significant difference in absolute changes in BP levels was observed among the genotypes in either treatment group.</p><p><b>CONCLUSION</b>The GNB3 C825T splice variant is associated with the DBP-lowering effect of telmisartan but not amlodipine in Chinese EH patients.</p>


Subject(s)
Adult , Aged , Amlodipine , Therapeutic Uses , Antihypertensive Agents , Therapeutic Uses , Benzimidazoles , Therapeutic Uses , Benzoates , Therapeutic Uses , Blood Pressure , Essential Hypertension , Female , Genotype , Heterotrimeric GTP-Binding Proteins , Genetics , Humans , Hypertension , Drug Therapy , Genetics , Male , Middle Aged , Polymorphism, Genetic , Genetics , Polymorphism, Restriction Fragment Length , Genetics
13.
Article in English | WPRIM | ID: wpr-285226

ABSTRACT

The aim of this study was to investigate the possible beneficial role of telmisartan in cerebral edema after traumatic brain injury (TBI) and the potential mechanisms related to the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) pyrin domain-containing 3 (NLRP3) inflammasome activation. TBI model was established by cold-induced brain injury. Male C57BL/6 mice were randomly assigned into 3, 6, 12, 24, 48 and 72 h survival groups to investigate cerebral edema development with time and received 0, 5, 10, 20 and 40 mg/kg telmisartan by oral gavage, 1 h prior to TBI to determine the efficient anti-edemic dose. The therapeutic window was identified by post-treating 30 min, 1 h, 2 h and 4 h after TBI. Blood-brain barrier (BBB) integrity, the neurological function and histological injury were assessed, at the same time, the mRNA and protein expression levels of NLRP3 inflammasome, IL-1β and IL-18 concentrations in peri-contused brain tissue were measured 24 h post TBI. The results showed that the traumatic cerebral edema occurred from 6 h, reached the peak at 24 h and recovered to the baseline 72 h after TBI. A single oral dose of 5, 10 and 20 mg/kg telmisartan could reduce cerebral edema. Post-treatment up to 2 h effectively limited the edema development. Furthermore, prophylactic administration of telmisartan markedly inhibited BBB impairment, NLRP3, apoptotic speck-containing protein (ASC) and Caspase-1 activation, as well as IL-1β and IL-18 maturation, subsequently improved the neurological outcomes. In conclusion, telmisartan can reduce traumatic cerebral edema by inhibiting the NLRP3 inflammasome-regulated IL-1β and IL-18 accumulation.


Subject(s)
Animals , Benzimidazoles , Benzoates , Blood-Brain Barrier , Brain Edema , Drug Therapy , Genetics , Pathology , Brain Injuries, Traumatic , Drug Therapy , Genetics , Pathology , Caspase 1 , Gene Expression Regulation , Humans , Inflammasomes , Genetics , Interleukin-18 , Interleukin-1beta , Male , Mice , NLR Family, Pyrin Domain-Containing 3 Protein , Genetics , Signal Transduction
14.
National Journal of Andrology ; (12): 110-115, 2016.
Article in Chinese | WPRIM | ID: wpr-304742

ABSTRACT

<p><b>OBJECTIVE</b>To study the impact of the chloride channel dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) on the cytoskeleton of Sertoli cells in the mouse.</p><p><b>METHODS</b>TM4 Sertoli cells were cultured and treated with CFTR(inh)-172 at the concentrations of 1, 5, 10 and 20 μmol/L for 48 hours. Then the cytotoxicity of CFT(inh)-172 was assessed by CCK-8 assay, the expressions of F-actin and Ac-tub in the TM4 Sertoli cells detected by immunofluorescence assay, and those of N-cadherin, vimentin and vinculin determined by qPCR.</p><p><b>RESULTS</b>CFTR(inh)-172 produced cytotoxicity to the TM4 Sertoli cells at the concentration of 20 μmol/L. The expressions of F-actin and Ac-tub were decreased gradually in the TM4 Sertoli cells with the prolonging of treatment time and increasing concentration of CFTR(inh)-172 (P < 0.05). The results of qPCR showed that different concentrations of CFTR(inh)-172 worked no significant influence on the mRNA expressions of N-cadherin, vimentin and vinculin in the Sertoli cells.</p><p><b>CONCLUSION</b>The CFTR chloride channel plays an important role in maintaining the normal cytoskeleton of Sertoli cells. The reduced function and expression of the CFTR chloride channel may affect the function of Sertoli cells and consequently spermatogenesis of the testis.</p>


Subject(s)
Actins , Metabolism , Animals , Benzoates , Pharmacology , Chloride Channels , Physiology , Cystic Fibrosis Transmembrane Conductance Regulator , Cytoskeleton , Male , Mice , Sertoli Cells , Metabolism , Spermatogenesis , Thiazolidines , Pharmacology , Time Factors
15.
Article in English | WPRIM | ID: wpr-277920

ABSTRACT

Objective To evaluate the clinical effectiveness of JianpiQinghua decoction in treating stage 3 chronic kidney disease (CKD3) with syndrome type of dampness-heat due to spleen deficiency. Methods A multicenter, randomized, controlled, prospective, double-blind, and double-simulation study was undertaken. A total of 270 CKD3 patients with syndrome type of dampness-heat due to spleen deficiency from the outpatient departments of six general hospitals were randomly divided into telmisartan+analog traditional Chinese medicine (TA) group, traditional Chinese medicine+analog telmisartan (TCMA) group, and telmisartan+traditional Chinese medicine (TTCM) group, in which the corresponding treatment was applied in addition to basic treatment. Six months later, changes in the traditional Chinese medicine (TCM) clinical symptom scores and renal functions before and after treatment were compared among these three groups. Results Of these 270 CKD3 patients who had been enrolled in this study, 30 cases lost to follow-up. The baseline data were comparable among these three groups. After treatment, the TCM clinical symptom scores of both syndrome of spleen-qi deficiency and dampness-heat in TA group were significantly higher than those in TCMA group and TTCM group (P<0.001). With the treatment time prolonged, the TCM clinical symptom scores showed similar descending trends in TCMA group and TTCM group but were different from that in TA group. After treatment, abnormal creatinine rate decreased (P=0.003), and these three treatments and their interactions with each visit had no effect on serum urea nitrogen value (P=0.270, P=0.520); with prolonged treatment, the estimated glomerular filtration rates in three groups tended to be relatively stable after the first rise. The liver function and abnormal serum potassium rate were not statistically significant before and after treatment (P>0.05). Conclusions JianpiQinghua decoction can improve clinical symptoms of TCM in CKD3 patients with syndrome type of dampness-heat due to spleen deficiency and thus improve the quality of life and prognosis. The clinical efficacy of JianpiQinghua decoction alone or combined with telmisartan is superior to telmisartan monotherapy.


Subject(s)
Benzimidazoles , Therapeutic Uses , Benzoates , Therapeutic Uses , Double-Blind Method , Drugs, Chinese Herbal , Therapeutic Uses , Humans , Medicine, Chinese Traditional , Phytotherapy , Prospective Studies , Quality of Life , Renal Insufficiency, Chronic , Drug Therapy
16.
Article in Chinese | WPRIM | ID: wpr-234043

ABSTRACT

<p><b>OBJECTIVE</b>To explore the efficacy and safety of deferasirox in aplastic anemia (AA)patients with iron overload.</p><p><b>METHODS</b>A single arm, multi- center, prospective, open- label study was conducted to evaluate absolute change in serum ferritin (SF)from baseline to 12 months of deferasirox administration, initially at a dose of 20 mg·kg(-1)·d(-1), and the safety in 64 AA patients with iron overload.</p><p><b>RESULTS</b>All patients started their deferasirox treatment with a daily dose of 20 mg · kg(-1) ·d(-1). The mean actual dose was (18.6±3.60) mg · kg(-1)·d(-1). The median SF decreased from 4 924 (2 718- 6 765)μg/L at baseline (n=64) to 3 036 (1 474- 5 551)μg/L at 12 months (n=23) with the percentage change from baseline as 38%. A median SF decrease of 651 (126-2 125)μg/L was observed at the end of study in 23 patients who completed 12 months' treatment, the median SF level decreased by 1 167(580-4 806)μg/L [5 271(3 420-8 278)μg/L at baseline; 3 036(1 474-5 551)μg/L after 12 months' treatment; the percentage change from baseline as 42% ] after 12 months of deferasirox treatment. The most common adverse events (AEs) were increased serum creatinine levels (40.98%), gastrointestinal discomfort (40.98%), elevated liver transaminase (ALT: 21.31%; AST: 13.11%)and proteinuria (24.59%). The increased serum creatinine levels were reversible and non-progressive. Of 38 patients with concomitant cyclosporine use, 12(31.8%)patients had two consecutive values >ULN, 10(26.3%)patients had two consecutive values >1.33 baseline values, but only 1(2.6%)patient's serum creatinine increased more than 1.33 baseline values and exceeded ULN. For both AST and ALT, no patients experienced two post- baseline values >5 ×ULN or >10 × ULN during the whole study. In AA patients with low baseline PLT count (less than 50 × 10(9)/L), there was no decrease for median PLT level during 12 months' treatment period.</p><p><b>CONCLUSIONS</b>AA patients with iron overload could achieve satisfactory efficacy of iron chelation by deferasirox treatment. The drug was well tolerated with a clinically manageable safety profile and no major adverse events.</p>


Subject(s)
Anemia, Aplastic , Drug Therapy , Benzoates , Therapeutic Uses , Blood Transfusion , China , Ferritins , Blood , Humans , Iron , Blood , Iron Chelating Agents , Therapeutic Uses , Iron Overload , Drug Therapy , Liver , Prospective Studies , Triazoles , Therapeutic Uses
17.
Chinese Medical Journal ; (24): 1894-1903, 2016.
Article in English | WPRIM | ID: wpr-251277

ABSTRACT

<p><b>BACKGROUND</b>The efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for immunoglobulin A nephropathy (IgAN) are unclear. This study was designed to evaluate the efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for IgAN.</p><p><b>METHODS</b>It is a multicenter, prospective, double-dummy randomized controlled trial. Primary IgAN patients were recruited in 13 renal units across Beijing, China, from July 2010 to June 2012. After a 4-week telmisartan (80 mg/d) wash-in, 400 patients continuing on 80 mg/d telmisartan were randomly assigned to additionally receive placebo (Group A), 50 mg/d clopidogrel (Group B), 20 mg/d leflunomide (Group C), or 50 mg/d clopidogrel and 20 mg/d leflunomide (Group D). The 24-week intervention was completed by 360 patients. The primary endpoint was change in 24-h proteinuria at 24 weeks. A linear mixed-effect model was used to analyze the changes at 4, 12, and 24 weeks. Generalized estimating equations were used to evaluate changes in hematuria grade. This trial was registered at the Chinese Clinical Trial Registry.</p><p><b>RESULTS</b>The effects of telmisartan combined with leflunomide on changes in proteinuria (0.36 [95% confidence interval (CI) 0.18-0.55] g/d, P < 0.001), in serum uric acid (76.96 [95% CI 57.44-96.49] μmol/L, P < 0.001), in serum creatinine (9.49 [95% CI 6.54-12.44] μmol/L, P < 0.001), and in estimated glomerular filtration rate (-6.72 [95% CI-9.46 to -3.98] ml·min-1·1.73 m-2, P < 0.001) were statistically significant, whereas they were not statistically significant on changes in systolic and diastolic blood pressure and weight (P > 0.05). Telmisartan combined with clopidogrel had no statistical effect on any outcome, and there was no interaction between the interventions. No obvious adverse reactions were observed.</p><p><b>CONCLUSIONS</b>Telmisartan combined with leflunomide, not clopidogrel, is safe and effective for decreasing proteinuria in certain IgAN patients.</p><p><b>TRIAL REGISTRATION</b>chictr.org.cn, ChiCTR-TRC-10000776; http://www.chictr.org.cn/showproj.aspx?proj=8760.</p>


Subject(s)
Adolescent , Adult , Benzimidazoles , Therapeutic Uses , Benzoates , Therapeutic Uses , Blood Pressure , China , Creatinine , Blood , Female , Glomerular Filtration Rate , Glomerulonephritis, IGA , Blood , Drug Therapy , Humans , Isoxazoles , Therapeutic Uses , Kidney Function Tests , Male , Middle Aged , Prospective Studies , Ticlopidine , Therapeutic Uses , Treatment Outcome , Uric Acid , Blood , Young Adult
19.
Article in English | WPRIM | ID: wpr-812471

ABSTRACT

Ischemic brain injury is a major disease which threatens human health and safety. (3, 5, 6-trimethylpyrazin-2-yl) methyl 3-methoxy-4-[(3, 5, 6-trimethylpyrazin-2-yl) methoxy] benzoate (VA-T), a newly discovered lead compound, is effective for the treatment of ischemic brain injury and its sequelae. But the poor solubility of VA-T leads to poor dissolution and limited clinical application. In order to improve the dissolution of VA-T, the pharmaceutical technology of solid dispersions was used in the present study. VA-T/polyvinylpyrrolidone (PVP) solid dispersion was prepared by the solvent method. The dissolution studies were carried out and solid state characterization was evaluated by differential scanning calorimetry (DSC), infrared spectroscopy (IR), x-ray diffraction (XRD) and scanning electron microscopy (SEM). The dissolution rate of VA-T was significantly improved by solid dispersion compared to that of the pure drug and physical mixture. The results of DSC and XRD indicated that the VA-T solid dispersion was amorphous. The IR spectra showed the possible interaction between VA-T and PVP was the formulation of hydrogen bonding. The SEM analysis demonstrated that there was no VA-T crystal observed in the solid dispersions. The ideal drug-to-PVP ratio was 1:5. In conclusion, the solid dispersion technique can be successfully used for the improvement of the dissolution profile of VA-T.


Subject(s)
Benzoates , Chemistry , Brain Ischemia , Drug Therapy , Chemistry, Pharmaceutical , Methods , Drug Delivery Systems , Povidone , Chemistry , Solubility
20.
Chinese Journal of Cardiology ; (12): 625-630, 2015.
Article in Chinese | WPRIM | ID: wpr-317704

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of angiotensin II (Ang II) antagonist telmisartan on retina vessel endothelial cell apoptosis and its impact on the ACE2-Ang-(1-7)-Mas axis in spontaneous hypertensive rats (SHR).</p><p><b>METHODS</b>Thirty-six SHR 16 week-old were randomly divided into 3 groups (n = 12 each): SHR, SHRT (telmisartan 10 mg · kg-1 · d-1 by gastric gavage) and SHRTA group (telmisartan 10 mg · kg-1 · d-1 by gastric gavage plus intravenous injection of A-779 0.5 mg · kg-1 · d-1), twelve WKY rats served as normotensive control group. Systolic blood pressure was measured at pre-treatment and 8 weeks later. After 8 weeks, rats were sacrificed, the expression of ACE2 and Mas in retina were analyzed by qRT-PCR, Western blot and Immunohistochemistry, the Ang-(1-7) concentration in serum was measured by ELISA. Specimens were obtained and stained by hematoxylin and eosin, and the morphology of retina vessel was observed. Apoptosis of vessel endothelial cells were determined by using terminal deoxynucleotidyl transferase mediated dUTP nick end labeling method.</p><p><b>RESULTS</b>The systolic blood pressure of SHR, SHRT and SHRTA groups at baseline were significantly higher than age-matched WKY group (all P < 0.01). Eight weeks later, the systolic blood pressure group was significantly lower in SHRT group than in the SHR group (P < 0.01), this effect was partly reversed in SHRTA group. The retinal ACE2 mRNA and protein expression was significantly lower in SHR group than in WKY and SHRT groups (P < 0.01), which was similar between SHRT group and SHRTA group (P > 0.05). The retinal Mas mRNA and protein expression were significantly lower in SHR group compared to WKY and SHRT groups (all P < 0.01), which was significantly lower in SHRTA group than in the SHRT group (P < 0.05). ELISA results showed that serum Ang-(1-7) protein level was significantly lower in SHR group than in WKY group and SHRT group (both P < 0.05), which was lower in SHRTA group compared to SHRT group. Retinal vessel endothelial cell apoptosis was higher in SHR group than in WKY group, which could be reduced by cotreatment with telmisartan and this beneficial effect could be reversed by A-779.</p><p><b>CONCLUSION</b>Telmisartan can reduce retinal vessel endothelial cell apoptosis via upregulating the ACE2-Ang-(1-7)-Mas axis.</p>


Subject(s)
Angiotensin I , Metabolism , Angiotensin II , Angiotensin II Type 1 Receptor Blockers , Pharmacology , Animals , Apoptosis , Benzimidazoles , Pharmacology , Benzoates , Pharmacology , Blood Pressure , Endothelial Cells , Peptide Fragments , Metabolism , Peptidyl-Dipeptidase A , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Retina , Systole , Up-Regulation
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