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1.
Korean Journal of Legal Medicine ; : 126-140, 2018.
Article in Korean | WPRIM | ID: wpr-740689

ABSTRACT

The diagnosis of cause of death (COD) or estimation of postmortem interval (PMI) is hard to perform using postmortem blood or other bodily fluids due to various biochemical changes that occur during the agonal phase or after death. To solve these problems, new paradigms and new analytical methods are needed. In this study, postmortem blood was fractionated with specific gravity 1.021, 1.029, 1.038, and 1.045, and the absorbance patterns of each sample of the 131 total cases (12 kinds of COD) were analyzed using a spectrometer. The absorbance was grouped into 9 patterns (ABS pattern 1 to 9) according to the wave length and the signal intensity. These patterns of postmortem blood were found to be distinctly different from the absorbance pattern of fresh blood. The analysis of ABS patterns is useful for the diagnosis of deaths due to acute or rapid bleeding, fire death, drowning and, in some cases, poisoning, but is not useful for the estimation of PMI.


Subject(s)
Cause of Death , Diagnosis , Drowning , Felodipine , Fires , Hemorrhage , Poisoning , Specific Gravity , Spectrum Analysis
2.
Translational and Clinical Pharmacology ; : 115-117, 2018.
Article in English | WPRIM | ID: wpr-742414

ABSTRACT

This tutorial explains the basic principles of mechanistic ligand-receptor interaction model, which is an operational model of agonism. A growing number of agonist drugs, especially immune oncology drugs, is currently being developed. In this tutorial, time-dependent ordinary differential equation for simple E(max) operational model of agonism was derived step by step. The differential equation could be applied in a pharmacodynamic modeling software, such as NONMEM, for use in non-steady state experiments, in which experimental data are generated while the interaction between ligand and receptor changes over time. Making the most of the non-steady state experimental data would simplify the experimental processes, and furthermore allow us to identify more detailed kinetics of a potential drug. The operational model of agonism could be useful to predict the optimal dose for agonistic drugs from in vitro and in vivo animal pharmacology experiments at the very early phase of drug development.


Subject(s)
Animals , Felodipine , In Vitro Techniques , Kinetics , Pharmacology
3.
Journal of Movement Disorders ; : 92-95, 2017.
Article in English | WPRIM | ID: wpr-38086

ABSTRACT

A 21-year-old male was admitted with severe right arm and hand tremors after a thalamic hemorrhage caused by a traffic accident. He was also suffering from agonizing pain in his right shoulder that manifested after the tremor. Neurologic examination revealed a disabling, severe, and irregular kinetic and postural tremor in the right arm during target-directed movements. There was also an irregular ipsilateral rest tremor and dystonic movements in the distal part of the right arm. The amplitude was moderate at rest and extremely high during kinetic and intentional movements. The patient underwent left globus pallidum internus and ventral intermediate thalamic nucleus deep brain stimulation. The patient improved by more than 80% as rated by the Fahn-Tolosa-Marin Tremor Rating Scale and Visual Analog Scale six months after surgery.


Subject(s)
Humans , Male , Young Adult , Accidents, Traffic , Arm , Deep Brain Stimulation , Felodipine , Globus Pallidus , Hand , Hemorrhage , Neurologic Examination , Shoulder Pain , Shoulder , Tremor , Visual Analog Scale
4.
Journal of Lipid and Atherosclerosis ; : 1-7, 2017.
Article in English | WPRIM | ID: wpr-175108

ABSTRACT

Bile acid has been well known to serve as a hormone in regulating transcriptional activity of Farnesoid X receptor (FXR), an endogenous bile acid nuclear receptor. Moreover, bile acid regulates diverse biological processes, including cholesterol/bile acid metabolism, glucose/lipid metabolism and energy expenditure. Alteration of bile acid metabolism has been revealed in type II diabetic (T2D) patients. FXR-mediated bile acid signaling has been reported to play key roles in improving metabolic parameters in vertical sleeve gastrectomy surgery, implying that FXR is an essential modulator in the metabolic homeostasis. Using a genetic mouse model, intestinal specific FXR-null mice have been reported to be resistant to diet-induced obesity and insulin resistance. Moreover, intestinal specific FXR agonism using gut-specific FXR synthetic agonist has been shown to enhance thermogenesis in brown adipose tissue and browning in white adipose tissue to increase energy expenditure, leading to reduced body weight gain and improved insulin resistance. Altogether, FXR is a potent therapeutic target for the treatment of metabolic diseases.


Subject(s)
Animals , Humans , Mice , Adipose Tissue, Brown , Adipose Tissue, White , Bile Acids and Salts , Bile , Biological Phenomena , Body Weight , Energy Metabolism , Felodipine , Gastrectomy , Homeostasis , Insulin Resistance , Metabolic Diseases , Metabolism , Obesity , Thermogenesis
5.
Biomolecules & Therapeutics ; : 12-25, 2017.
Article in English | WPRIM | ID: wpr-165941

ABSTRACT

G protein-coupled receptors (GPCRs) are a family of cell-surface proteins that play critical roles in regulating a variety of pathophysiological processes and thus are targeted by almost a third of currently available therapeutics. It was originally thought that GPCRs convert extracellular stimuli into intracellular signals through activating G proteins, whereas β-arrestins have important roles in internalization and desensitization of the receptor. Over the past decade, several novel functional aspects of β-arrestins in regulating GPCR signaling have been discovered. These previously unanticipated roles of β-arrestins to act as signal transducers and mediators of G protein-independent signaling have led to the concept of biased agonism. Biased GPCR ligands are able to engage with their target receptors in a manner that preferentially activates only G protein- or β-arrestin-mediated downstream signaling. This offers the potential for next generation drugs with high selectivity to therapeutically relevant GPCR signaling pathways. In this review, we provide a summary of the recent studies highlighting G protein- or β-arrestin-biased GPCR signaling and the effects of biased ligands on disease pathogenesis and regulation.


Subject(s)
Humans , Bias , Felodipine , GTP-Binding Proteins , Ligands , Pathology , Physiology , Transducers
6.
Journal of Dental Hygiene Science ; (6): 249-255, 2016.
Article in Korean | WPRIM | ID: wpr-655302

ABSTRACT

The Ministry of Health and Welfare in Korea has enforced the oral health promotion program for elderly in Korea. There are the denture delivery program and the fluoride application-scaling program for elderly. Donggu Public Health Center in Daejeon has delivered the fluoride application- scaling program for elderly since the demonstration project in 2009. The official dental hygienists had a prior consultation with Dong-gu branch of Korean Senior Citizens Association in Daejeon. We expanded the program through government office, welfare centers, and nursing homes. The participants were satisfied with the public relations (95.2%), scaling (99.7%), fluoride application (91.5%), toothbrushing education (98.6%), and denture cleaning education (96.6%). After a medial accident with persistent bleeding, the pre-inspection survey about systemic disease and medication was reinforced. The official dental hygienists have agonized over the low participation of the low-income group and the overlap benefit with health insurance benefit of scaling. We suggested it be needed the assessment of the public oral health program to overlap with health insurance benefit.


Subject(s)
Aged , Humans , Dental Hygienists , Dentures , Education , Felodipine , Fluorides , Hemorrhage , Insurance, Health , Korea , Nursing Homes , Oral Health , Public Health , Public Relations , Toothbrushing
7.
Journal of Rheumatic Diseases ; : 332-335, 2016.
Article in English | WPRIM | ID: wpr-81679

ABSTRACT

Serotonin syndrome, an adverse drug reaction, is a consequence of excess serotonergic agonism of central nervous system receptors and peripheral serotonergic receptors. Serotonin syndrome has been associated with large numbers of drugs and drug combinations, and serotonin-norepinephrine reuptake inhibitor-induced serotonin syndrome is rare. It is often described as a sign of excess serotonin ranging from tremor in mild cases to delirium, neuromuscular rigidity, and hyperthermia in life-threatening cases. Diagnosis is based on the symptoms and patient's history, and several diagnostic criteria have been developed. We experienced a rare case of fibromyalgia accompanied by tremor, hyperreflexia, spontaneous clonus, muscle rigidity, and diaphoresis after 10 days of single use of duloxetine 30 mg. Only one case of serotonin syndrome resulting from administration of duloxetine has been reported in Korea, however that case resulted from co-administration of fluoxetine. We report here on this case along with a review of the relevant literature.


Subject(s)
Humans , Central Nervous System , Delirium , Diagnosis , Drug Combinations , Drug-Related Side Effects and Adverse Reactions , Duloxetine Hydrochloride , Felodipine , Fever , Fibromyalgia , Fluoxetine , Korea , Muscle Rigidity , Reflex, Abnormal , Serotonin Syndrome , Serotonin , Tremor
8.
Clinical Psychopharmacology and Neuroscience ; : 405-406, 2016.
Article in English | WPRIM | ID: wpr-160415

ABSTRACT

The selective melatonin receptor agonism effect of ramelteon is useful for insomnia. Here we wanted to present a refractory chronic migraine case, who had significant improvements in migraine after using ramelteon. The possible mechanism for the ramelteon in the migraine relief might be related to melatonin effects.


Subject(s)
Felodipine , Melatonin , Migraine Disorders , Receptors, Melatonin , Sleep Initiation and Maintenance Disorders , Sleep Wake Disorders
9.
Dementia and Neurocognitive Disorders ; : 103-109, 2016.
Article in English | WPRIM | ID: wpr-111905

ABSTRACT

Depression is a relatively common agonizing psychiatric disorder that affects the way we feel and think about ourselves and the world around us. Cognitive theories of depression have long posited that various cognitive biases are involved in the development and recurrence of depression. However, the current cognitive theory of depression has been reformulated and expanded from the previous cognitive model of depression based on the results from pharmacological, neuroimaging and neurocognitive studies. This review summarizes the evidence for cognitive dysfunctions in depression and the related pharmacological, neuroanatomical and genetic aspects which aim to integrate our knowledge about the cognitive aspects of depression and its treatment. The newly formulated cognitive theory of depression provides directions for future investigation to identify people at risk, to minimize recurrence, and to maximize long-term beneficial outcomes for those suffering from depression.


Subject(s)
Bias , Cognition , Depression , Felodipine , Neuroimaging , Recurrence
10.
Korean Journal of Legal Medicine ; : 55-60, 2016.
Article in English | WPRIM | ID: wpr-101307

ABSTRACT

Postmortem bacterial culture can be valuable for investigating deaths and determining the cause of death. However, there are many concerns regarding postmortem bacterial culture such as postmortem transmigration and agonal spread of bacteria. The two main methods for identification of the bacteria are biochemical and genetic methods. In Korea, the genetic method has been used for postmortem bacterial culture and identification in forensic medicine. However, there is a lack of consensus on the method to be used for postmortem bacterial culture and identification. Herein, we compared the genetic and biochemical methods of postmortem bacterial culture in autopsy practice. Both analyses were performed on the same samples. Bacteria were identified in 28 of the 34 cases (82.4%). Of the 74 comparable samples, only 28 (37.8%) showed consistent results by both methods. In addition, the biochemical method had a shorter reporting time and was more sensitive. In conclusion, we analyzed the causes of the inconsistency between the two methods and provided appropriate conditions and protocols for postmortem bacterial culture and identification.


Subject(s)
Autopsy , Bacteria , Biochemical Phenomena , Cause of Death , Consensus , Felodipine , Forensic Medicine , Genetic Phenomena , Korea , Methods
11.
The Korean Journal of Physiology and Pharmacology ; : 413-420, 2015.
Article in English | WPRIM | ID: wpr-727356

ABSTRACT

Dexmedetomidine is a sedative and analgesic agent that exerts its effects by selectively agonizing alpha2 adrenoceptor. Histamine is a pathophysiological amine that activates G protein-coupled receptors, to induce Ca2+ release and subsequent mediate or progress inflammation. Dexmedetomidine has been reported to exert inhibitory effect on inflammation both in vitro and in vivo studies. However, it is unclear that dexmedetomidine modulates histamine-induced signaling and pro-inflammatory cytokine expression. This study was carried out to assess how dexmedetomidine modulates histamine-induced Ca2+ signaling and regulates the expression of pro-inflammatory cytokine genes encoding interleukin (IL)-6 and -8. To elucidate the regulatory role of dexmedetomidine on histamine signaling, HeLa cells and human salivary gland cells which are endogenously expressed histamine 1 receptor were used. Dexmedetomidine itself did not trigger Ca2+ peak or increase in the presence or absence of external Ca2+. When cells were stimulated with histamine after pretreatment with various concentrations of dexmedetomidine, we observed inhibited histamine-induced [Ca2+]i signal in both cell types. Histamine stimulated IL-6 mRNA expression not IL-8 mRNA within 2 hrs, however this effect was attenuated by dexmedetomidine. Collectively, these findings suggest that dexmedetomidine modulates histamine-induced Ca2+ signaling and IL-6 expression and will be useful for understanding the antagonistic properties of dexmedetomidine on histamine-induced signaling beyond its sedative effect.


Subject(s)
Humans , Dexmedetomidine , Felodipine , HeLa Cells , Histamine , Hypnotics and Sedatives , Inflammation , Interleukin-6 , Interleukin-8 , Interleukins , RNA, Messenger , Salivary Glands
12.
Anesthesia and Pain Medicine ; : 267-270, 2015.
Article in English | WPRIM | ID: wpr-149869

ABSTRACT

Serotonin syndrome is an unexpected adverse reaction of serotonergic medication. Some drugs used by anesthesiologists may cause serotonin syndrome. Serotonin syndrome is known to be related to 5-hydroxytryptamine 1A and 5-hydroxytryptamine 2A agonism. However, recent research has revealed evidence that 5-hydroxytryptamine 3 (5-HT3) antagonism can also play a role in serotonin syndrome. Among the 5-HT3 antagonists, palonosetron is the most highly specific. In this study, we present the first case of fentanyl- and meperidine-induced serotonin syndrome precipitated by palonosetron in general anesthesia.


Subject(s)
Anesthesia, General , Felodipine , Fentanyl , Meperidine , Serotonin 5-HT3 Receptor Antagonists , Serotonin Syndrome , Serotonin
13.
Biomolecules & Therapeutics ; : 218-224, 2015.
Article in English | WPRIM | ID: wpr-178042

ABSTRACT

Endocannabinoids can affect multiple cellular targets, such as cannabinoid (CB) receptors, transient receptor potential cation channel, subfamily V, member 1 (TRPV1) and peroxisome proliferator-activated receptor gamma (PPARgamma). The stimuli to induce adipocyte differentiation in hBM-MSCs increase the gene transcription of the CB1 receptor, TRPV1 and PPARgamma. In this study, the effects of three endocannabinoids, N-arachidonoyl ethanolamine (AEA), N-arachidonoyl dopamine (NADA) and 2-arachidonoyl glycerol (2-AG), on adipogenesis in hBM-MSCs were evaluated. The adipocyte differentiation was promoted by AEA whereas inhibited by NADA. No change was observed by the treatment of non-cytotoxic concentrations of 2-AG. The difference between AEA and NADA in the regulation of adipogenesis is associated with their effects on PPARgamma transactivation. AEA can directly activate PPARgamma. The effect of AEA on PPARgamma in hBM-MSCs may prevail over that on the CB1 receptor mediated signal transduction, giving rise to the AEA-induced promotion of adipogenesis. In contrast, NADA had no effect on the PPARgamma activity in the PPARgamma transactivation assay. The inhibitory effect of NADA on adipogenesis in hBM-MSCs was reversed not by capsazepine, a TRPV1 antagonist, but by rimonabant, a CB1 antagonist/inverse agonist. Rimonabant by itself promoted adipogenesis in hBM-MSCs, which may be interpreted as the result of the inverse agonism of the CB1 receptor. This result suggests that the constantly active CB1 receptor may contribute to suppress the adipocyte differentiation of hBM-MSCs. Therefore, the selective CB1 agonists that are unable to affect cellular PPARgamma activity inhibit adipogenesis in hBM-MSCs.


Subject(s)
Humans , Adipocytes , Adipogenesis , Dopamine , Endocannabinoids , Ethanolamine , Felodipine , Glycerol , Mesenchymal Stem Cells , PPAR gamma , Receptor, Cannabinoid, CB1 , Receptors, Cannabinoid , Signal Transduction , Transcriptional Activation
14.
Rev. latinoam. enferm ; 22(6): 893-901, 16/12/2014. tab, graf
Article in English | LILACS | ID: lil-732955

ABSTRACT

OBJECTIVES: to analyze the Pelvic Floor Muscle Strength (PFMS) of pregnant women with one or more vaginal or cesarean deliveries; to compare the PFMS of these with pregnant women with the PFMS of primiparous women. METHODS: cross-sectional study with women up to 12 weeks pregnant, performed in Itapecerica da Serra, São Paulo state, from December 2012 to May 2013. The sample consisted of 110 pregnant women with one or more vaginal deliveries or cesarean sections and 110 primigravidae. The PFMS was evaluated by perineometry (Peritron(tm)) and vaginal digital palpation (modified Oxford scale). RESULTS: the average PFMS in pregnant women with a history of vaginal delivery or cesarean section was 33.4 (SD=21.2) cmH2O. From the Oxford scale, 75.4% of the pregnant women with previous vaginal or cesarean deliveries presented grade ≤ 2, and 5.5% grade ≥ 4; among the primiparae, 39.9% presented grade ≤ 2, and 50.9% grade ≥ 4, with a statistically significant difference (p<0.001). From the perineometry, there was no statistically significant difference between the PFMS and age, type of delivery, parity, body mass index, and genitourinary tract symptoms, however, there was a statistically significant difference between the pregnant women with and without a history of episiotomy (p=0.04). In the palpation, none of the variables showed a statistically significant difference. CONCLUSION: pregnancy and childbirth can reduce the PFMS. .


OBJETIVOS: analisar a força muscular do assoalho pélvico de gestantes com um ou mais partos normais ou cesarianas; comparar a a força muscular do assoalho pélvico dessas gestantes com a de primigestas. MÉTODO: estudo transversal com gestantes até 12 semanas de gravidez, realizado em Itapecerica da Serra, SP, de dezembro de 2012 a maio de 2013. A amostra foi composta por 110 gestantes, com um ou mais partos normais ou cesarianas e 110 primigestas. A força muscular do assoalho pélvico foi avaliada pela perineometria e palpação digital vaginal (Escala de Oxford modificada). RESULTADOS: a média da força muscular do assoalho pélvico em gestantes com antecedentes de parto normal ou cesariana foi 33,4 (desvio-padrão=21,2) cmH2O. Pela escala de Oxford, 75,4% das gestantes com partos ou cesarianas anteriores apresentaram grau ≤2 e 5,5%, grau ≥4; entre as primigestas, 39,9% apresentaram grau ≤2 e 50,9%, grau ≥4, com diferença estatisticamente significante (p<0,001). Pela perineometria, não houve diferença estatisticamente significante entre a força muscular do assoalho pélvico e idade, tipo de parto, paridade, índice de massa corpórea e sintomas do trato geniturinário, mas houve entre as gestantes com e sem antecedente de episiotomia (p=0,04). Na palpação, nenhuma das variáveis mostrou diferença estatisticamente significante. CONCLUSÃO: a gravidez e o parto podem reduzir a força muscular do assoalho pélvico. .


OBJETIVOS: analizar la Fuerza Muscular del Suelo Pélvico (FMSP) de embarazadas con uno o más partos normales o cesáreas; comparar la FMSP de estas embarazadas con la FMSP de primigestas. MÉTODO: estudio transversal con embarazadas hasta 12 semanas de embarazo, realizado en Itapecerica de la Serra, SP, de diciembre de 2012 a mayo de 2013. La muestra fue de 110 embarazadas con uno o más partos normales o cesáreas y 110 primigestas. La FMSP fue evaluada por la perineometría (Peritron(tm)) y palpación digital vaginal (escala de Oxford modificada). RESULTADOS: el promedio de la FMSP en embarazadas con antecedentes de parto normal o cesárea fue 33,4 (de=21,2) cmH2O. Por la escala de Oxford, 75,4% de las embarazadas con partos o cesáreas anteriores presentaron grado ≤ 2 y 5,5%, grado ≥ 4; entre las primigestas, 39,9% presentaron grado ≤ 2 y 50,9%, grado ≥ 4, con diferencia estadísticamente significativa (p<0,001). Por la perineometría, no hubo diferencia estadísticamente significativa entre la FMSP y edad, tipo de parto, número de partos anteriores, índice de masa corporal y síntomas del tracto genitourinario, pero hubo entre las embarazadas con y sin antecedente de episiotomía (p=0,04). En la palpación, ninguna de las variables mostró diferencia estadísticamente significativa. CONCLUSIÓN: el embarazo y el parto pueden reducir la FMSP. .


Subject(s)
Calcium , Calmodulin , Calpain , Binding Sites , Calcium/pharmacology , Calmodulin/antagonists & inhibitors , Calpain/antagonists & inhibitors , Calpain/metabolism , Fluorescent Dyes , Felodipine/pharmacology , In Vitro Techniques , Imidazoles/pharmacology , Leucine/analogs & derivatives , Leucine/pharmacology , Molecular Conformation , Naphthalenesulfonates/pharmacology , Spectrometry, Fluorescence
15.
Braz. j. pharm. sci ; 50(1): 203-212, Jan-Mar/2014. tab, graf
Article in English | LILACS | ID: lil-709551

ABSTRACT

The objective of this research work was to design, develop and optimize the self micro-emulsifying drug delivery system (SMEDDS) of Felodipine (FL) filled in hard gelatine capsule coated with polymer in order to achieve rapid drug release after a desired time lag in the management of hypertension. Microemulsion is composed of a FL, Lauroglycol FCC, Transcutol P and Cremophor EL. The optimum surfactant to co-surfactant ratio was found to be 2:1. The resultant microemulsions have a particle size in the range of 65-85 nm and zeta potential value of -13.71 mV. FL release was adequately adjusted by using pH independent polymer i.e. ethyl cellulose along with dibutyl phthalate as plasticizer. Influence of formulation variables like viscosity of polymer, type of plasticizer and percent coating weight gain was investigated to characterize the time lag. The developed formulation of FL SMEDDS capsules coated with ethyl cellulose showed time lag of 5-7 h which is desirable for chronotherapeutic application.


O objetivo desse trabalho de pesquisa foi planejar, desenvolver e otimizar sistema de liberação de fármaco auto-microemulsificante(SMEDDS) de felodipino (FL) em cápsulas de gelatina dura revestidas com polímero, a fim de obter liberação rápida após tempo desejado no manejo da hipertensão. A microemulsão é composta de FL, lauroglilcol FCC, Transcutol P e Cremophor EL. A proporção ótima de tensoativo e de co-tensoativo foi de 2:1. As microemulsões resultantes têm tamanho de partícula na faixa de 65-85 nm com potencial zeta de -13,71 mV. A liberação de FL foi ajustada adequadamente, utilizando-se polímero independente de pH, como etilcelulose com ftalato de dibutila como plastificante. A influência das variáveis da formulação, como viscosidade do polímero, tipo de plastificante e ganho percentual de peso do revestimento foi investigada para caracterizar o intervalo de tempo de liberação. A formulação de cápsulas de FL SMEDDS revestidas com etilcelulose mostrou intervalo de tempo de liberação de 5 a 7 horas, o que é desejável para uma aplicação cronoterapêutica.


Subject(s)
Felodipine/pharmacokinetics , Drug Liberation/drug effects , Emulsifying Agents/pharmacokinetics , Emulsions/pharmacokinetics , Drug Chronotherapy , Hypertension/prevention & control
16.
China Journal of Chinese Materia Medica ; (24): 381-385, 2013.
Article in Chinese | WPRIM | ID: wpr-346812

ABSTRACT

<p><b>OBJECTIVE</b>To explore the effect of puerarin combined with felodipine on the mRNA and protein expression of apelin and APJ in renal tissue of renovascular hypertensive rat.</p><p><b>METHOD</b>Sixty-two Sprague-Dawley rats were used, of which 8 rats were randomly chosen as sham-operation group. The remaining rats were made for the rat model with renovascular hypertension. The renovascular hypertensive rats were randomly divided into 5 groups as follows: 4 groups which were treated with felodipine (0.8 mg x kg(-1) x d(-1)), puerarin (50 mg x kg(-1) x d(-1)), puerarin combined with felodipine (puerarin 25 mg x kg(-1) x d(-1) + felodipine 0.4 mg x kg(-1) x d(-1)) or captopril combined with felodipine (captopril 15 mg x kg(-1) x d(-1) x felodipine 0.4 mg x kg(-1) x d(-1)), and 1 group which was treated with distilled water. Drugs or distilled water were administered for 8 weeks. The expression of apelin and APJ mRNA and protein in ischemic and non-ischemic kidneys was assessed by RT-PCR or Western blot.</p><p><b>RESULT</b>Compared with sham-operation group, the expression of apelin mRNA and protein in ischemic and non-ischemic kidneys in model group was increased significantly (P < 0.01); the expression of APJ mRNA and protein in ischemic kidneys had no significance, while that in non-ischemic kidneys was decreased (P < 0. 01). Compared with model group, the expression of apelin mRNA and protein in ischemic and non-ischemic kidneys was decreased significantly in all drug-treated groups (P < 0.01); while that of APJ mRNA and protein in non-ischemic kidneys was upregulated (P < 0.01). Compared with felodipine group, the expression of apelin mRNA and protein in ischemic and non-ischemic kidneys was decreased (P < 0.01 or P < 0.05) in the group treated with both puerarin and felodipine; and the expression of APJ mRNA and protein in ischemic kidneys did not reach significant level, however, that was upregulated in non-ischemic kidneys (P < 0.01 or P < 0.05).</p><p><b>CONCLUSION</b>Puerarin downregulates the expression of apelin mRNA and protein in ischemic and non-ischemic kidneys, and upregulates that of APJ mRNA and protein in non-ischemic kidneys. Combination of puerarin and felodipine enhances the above-mentioned effects and shows no significant difference versus the combination of felodipine and captopril. The results suggest that puerarin regulates blood pressure and protects target organ through apelin/APJ pathway and that puerarin has synergetic effects with CCB.</p>


Subject(s)
Animals , Male , Rats , Antihypertensive Agents , Pharmacology , Apelin , Apelin Receptors , Blotting, Western , Captopril , Pharmacology , Drug Synergism , Felodipine , Pharmacology , Gene Expression , Hypertension, Renovascular , Genetics , Metabolism , Intercellular Signaling Peptides and Proteins , Genetics , Metabolism , Ischemia , Isoflavones , Pharmacology , Kidney , Metabolism , RNA, Messenger , Genetics , Metabolism , Random Allocation , Rats, Sprague-Dawley , Receptors, G-Protein-Coupled , Genetics , Metabolism , Reverse Transcriptase Polymerase Chain Reaction , Vasodilator Agents , Pharmacology
17.
Psychiatry Investigation ; : 200-202, 2013.
Article in English | WPRIM | ID: wpr-42586

ABSTRACT

Sexual dysfunction is a common side effect in patients treated with antipsychotics but significant differences exist across different compounds. We report hypersexuality symptoms in two female patients with schizophrenia who were receiving treatment with aripiprazole. The patients experienced more frequent sexual desire and greater sexual preoccupation after taking aripiprazole. We discuss the potential neuro-chemical mechanisms for this and argue that aripiprazole's unique pharmacological profile, partial agonism with high affinity at dopamine D2-receptor, may have contributed to the development of these symptoms.


Subject(s)
Female , Humans , Antipsychotic Agents , Dopamine , Felodipine , Piperazines , Quinolones , Schizophrenia , Aripiprazole
18.
Genomics & Informatics ; : 282-288, 2013.
Article in English | WPRIM | ID: wpr-84015

ABSTRACT

The molecular vibration-activity relationship in the receptor-ligand interaction of adenosine receptors was investigated by structure similarity, molecular vibration, and hierarchical clustering in a dataset of 46 ligands of adenosine receptors. The resulting dendrogram was compared with those of another kind of fingerprint or descriptor. The dendrogram result produced by corralled intensity of molecular vibrational frequency outperformed four other analyses in the current study of adenosine receptor agonism and antagonism. The tree that was produced by clustering analysis of molecular vibration patterns showed its potential for the functional classification of adenosine receptor ligands.


Subject(s)
Adenosine , Classification , Dataset , Dermatoglyphics , Felodipine , Ligands , Receptors, G-Protein-Coupled , Receptors, Purinergic P1 , Subject Headings , Vibration
19.
Biomolecules & Therapeutics ; : 29-34, 2013.
Article in English | WPRIM | ID: wpr-28628

ABSTRACT

The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor family of cytokines. TRAIL selectively induces apoptotic cell death in various tumors and cancer cells, but it has little or no toxicity in normal cells. Agonism of TRAIL receptors has been considered to be a valuable cancer-therapeutic strategy. However, more than 85% of primary tumors are resistant to TRAIL, emphasizing the importance of investigating how to overcome TRAIL resistance. In this report, we have found that nemadipine-A, a cell-permeable L-type calcium channel inhibitor, sensitizes TRAIL-resistant cancer cells to this ligand. Combination treatments using TRAIL with nemadipine-A synergistically induced both the caspase cascade and apoptotic cell death, which were blocked by a pan caspase inhibitor (zVAD) but not by autophagy or a necrosis inhibitor. We further found that nemadipine-A, either alone or in combination with TRAIL, notably reduced the expression of survivin, an inhibitor of the apoptosis protein (IAP) family of proteins. Depletion of survivin by small RNA interference (siRNA) resulted in increased cell death and caspase activation by TRAIL treatment. These results suggest that nemadipine-A potentiates TRAIL-induced apoptosis by down-regulation of survivin expression in TRAIL resistant cells. Thus, combination of TRAIL with nemadipine-A may serve a new therapeutic scheme for the treatment of TRAIL resistant cancer cells, suggesting that a detailed study of this combination would be useful.


Subject(s)
Humans , Apoptosis , Autophagy , Calcium Channels, L-Type , Cell Death , Cytokines , Down-Regulation , Felodipine , Necrosis , Receptors, TNF-Related Apoptosis-Inducing Ligand , RNA Interference , Tumor Necrosis Factor-alpha
20.
Acta Pharmaceutica Sinica ; (12): 223-228, 2012.
Article in Chinese | WPRIM | ID: wpr-323054

ABSTRACT

The paper reports the systematic study on felodipine and its impurities in tablets, to improve its quality standards for the control of the related substances. HPLC-DAD, UPLC-MS, IR and NMR methods were used for the isolation of felodipine and its impurities in tablets, their identification and the zebrafish animal model was used for the analysis of the toxic impurities. In felodipine material and its tablets, three impurities are isolated and identified. They are impurity 1 [dimethyl 4-(2, 3-dichlorophenyl)-2, 6-dimethyl-1, 4-dihydropyridine-3, 5-dicarboxylate], impurity 2 [ethyl methyl 4-(2, 3-dichlorophenyl)-2, 6-dimethylpyridine-3, 5-dicarboxylate] and impurity 3 [diethyl 4-(2, 3-dichlorophenyl)-2, 6-dimethyl-1, 4-dihydropyridine-3, 5-dicarboxylate], separately. The result of zebrafish animal model analysis showed that the teratogenic effects of four compounds were: impurity 3 > or = felodipine > impurity 1 > impurity 2, lethal effects were as follows: impurity 2 = impurity 3 > felodipine > or = impurity 1. This study confirmed the toxicity of three impurities in felodipine. According to the results, the paper suggested the amendments to the standard of the medicine and provided the support to the control of impurities in the manufacturing process.


Subject(s)
Animals , Abnormalities, Drug-Induced , Antihypertensive Agents , Chemistry , Toxicity , Calcium Channel Blockers , Chemistry , Toxicity , Chromatography, High Pressure Liquid , Methods , Drug Contamination , Felodipine , Chemistry , Toxicity , Magnetic Resonance Spectroscopy , Molecular Structure , Pharmaceutical Preparations , Chemistry , Quality Control , Spectrophotometry, Infrared , Tablets , Tandem Mass Spectrometry , Zebrafish
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