• Title/Summary/Keyword: drug substance

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Effect of Acupuncture(PC6) on Behavior, Dopamine Release in the Nucleus Accumbens in Rats Sensitized to Morphine (몰핀에 민감화된 흰쥐의 내관부위 자침이 행동과 측핵의 도파민 유리에 미치는 효과)

  • Kim, Sang-Ho;Lyu, Seung-Jun;Kim, Tae-Heon;Kang, Hyung-Won;Lyu, Yeoung-Su
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.19 no.4
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    • pp.982-992
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    • 2005
  • Acupuncture as a therapeutic intervention is widely used for the treatment of many functional disorders such as substance abuse and mental dysfunction. Clinical trials are currently underway to determine the effectiveness of acupuncture in the treatment of drug addiction. Yet, there are still many unanswered questions about the basic mechanism of acupuncture. Studies have shown that both the psychomotor stimulant effects and rewarding properties of addictive drugs, including morphine, are sensitized by repeated drug administration and raised the possibility that both of these effects may De linked to the same or closely overlapping the mesolimbic dopamine systems. Neiguan (PC6) point on the pericardium channel which is associated with the brain and its mental function, has been used to treat mental, psychosomatic disorders and gastroenterological disorders. The present study was designed to investigate the effect of acupuncture on repeated morphine-induced changes in extracellular dopamine levels using in vivo microdialysis and to measure the effect of acupuncture on repeated morphine-induced behavioral changes. Male Sprague-Dawley rats were treated twice a day for three days with increasing doses of morphine (10, 20 and 40 mg/kg, s.c.) or with saline. After 15 days of withdrawal, rats were challenged with morphine hydrochloride (5 mg/kg, s.c.). Acupuncture was applied at bilateral Neiguan (PC6) points for 1min after the morphine challenge. Results showed that acupuncture at the specific acupoint PC6, but not at control points (tail and HE8) significantly decreased both dopamine release, behavior induced by a systemic morphine challenge or a single s.c. morphine injection in the morphine-repeated animals. These results suggest that reduction in sensitization may be one mechanism whereby acupuncture alleviates morphine craving in addicts. Moreover, in a more general sense these results suggest that acupuncture can be used as a therapeutic intervention for correcting reversible malfunction of the body by direction of brain pathway and thus acupuncture can contribute to the biochemical balance in the central nervous system by regulating neurotransmitters.

Analytical methods to manage potential impurities in drug substances (의약품 중 잠재적 불순물 관리를 위한 분석법 연구 동향)

  • Park, Kyung Min;Kim, Won Mi;Ahn, Su Hyun;Lee, Ha Lim;Hwang, Su Hyeon;Lee, Wonwoong;Hong, Jongki
    • Analytical Science and Technology
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    • v.35 no.3
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    • pp.93-115
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    • 2022
  • Potential impurities in pharmaceuticals could be produced during manufacture, distribution, and storage and affect quality and safety of pharmaceuticals. In particular, highly reactive impurities could result in carcinogenic (mutagenic) effects on human body. International Conference on Harmonisation (ICH) has provided M7(R1) guideline for "Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk" and recommended an adoption of this guideline to the authorities. ICH M7(R1) guideline provides classification, accepted intakes, and controls of potential impurities in pharmaceuticals. However, since appropriate and unified analytical methods for impurities in pharmaceuticals have not been provided in this guideline, most potential impurities in pharmaceuticals are still difficult to manage and supervise by pharmaceutical companies and regulatory authorities, respectively. In this review, we briefly described definition of unintended mutagenic impurities, basic information in ICH M7(R1) guideline, and analytical methods to determine potential impurities. This review would be helpful to manage and supervise potential impurities in pharmaceuticals by pharmaceutical companies and regulatory authorities.

Network pharmacology-based prediction of efficacy and mechanism of Chongmyunggongjin-dan acting on Alzheimer's disease (네트워크 약리학을 기반으로한 총명공진단(聰明供辰丹) 구성성분과 알츠하이머 타겟 유전자의 효능 및 작용기전 예측)

  • Bitna Kweon;Sumin Ryu;Dong-Uk Kim;Jin-Young Oh;Mi-Kyung Jang;Sung-Joo Park;Gi-Sang Bae
    • The Journal of Korean Medicine
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    • v.44 no.2
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    • pp.106-118
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    • 2023
  • Objectives: Network pharmacology is a method of constructing and analyzing a drug-compound-target network to predict potential efficacy and mechanisms related to drug targets. In that large-scale analysis can be performed in a short time, it is considered a suitable tool to explore the function and role of herbal medicine. Thus, we investigated the potential functions and pathways of Chongmyunggongjin-dan (CMGJD) on Alzheimer's disease (AD) via network pharmacology analysis. Methods: Using public databases and PubChem database, compounds of CMGJD and their target genes were collected. The putative target genes of CMGJD and known target genes of AD were compared and found the correlation. Then, the network was constructed using Cytoscape 3.9.1. and functional enrichment analysis was conducted based on the Gene Ontology (GO) Biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathways to predict the mechanisms. Results: The result showed that total 104 compounds and 1157 related genes were gathered from CMGJD. The network consisted of 1157nodes and 10034 edges. 859 genes were interacted with AD gene set, suggesting that the effects of CMGJD are closely related to AD. Target genes of CMGJD are considerably associated with various pathways including 'Positive regulation of chemokine production', 'Cellular response to toxic substance', 'Arachidonic acid metabolic process', 'PI3K-Akt signaling pathway', 'Metabolic pathways', 'IL-17 signaling pathway' and 'Neuroactive ligand-receptor interaction'. Conclusion: Through a network pharmacological method, CMGJD was predicted to have high relevance with AD by regulating inflammation. This study could be used as a basis for effects of CMGJD on AD.

$\beta$-Glucan Suppresses LPS-stimulated NO Production Through the Down-regulation of iNOS Expression and $NF{\kappa}B$ Transactivation in RAW 264.7 Macrophages

  • Yang, Jeong-Lye;Jang, Ji-Hyun;Radhakrishnan, Vinodhkumar;Kim, Yang-Ha;Song, Young-Sun
    • Food Science and Biotechnology
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    • v.17 no.1
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    • pp.106-113
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    • 2008
  • The antioxidant and anti-inflammatory protective effects of $\beta$-glucan from barley on RAW 264.7 murine macrophage cells induced by lipopolysaccharide (LPS) were examined. The RAW 264.7 murine macrophages were preincubated with various concentrations ($0-200\;{\mu}g/mL$) of $\beta$-glucan and stimulated with LPS to induce oxidative stress and inflammation. The $\beta$-glucan treatments were found to reduce thiobarbituric acid-reactive substance (TBARS) accumulation, and enhance glutathione levels and the activities of antioxidative enzymes, including superoxide dismutase (SOD), catalase, glutathione reductase, and glutathione peroxidase (GSH-px) in the LPS-stimulated macrophages as compared to the LPS-only treated cells. Nitric oxide (NO) production was significantly suppressed in a dose-dependent manner (p<0.05) with an $IC_{50}$ of $104\;{\mu}g/mL$. Further treatment with $\beta$-glucan at $200\;{\mu}g/mL$ suppressed NO production to 2% of the LPS-control, and suppressed the levels of inducible nitric oxide synthase (iNOS) protein and mRNA in a dose-dependent manner. The specific DNA binding activity of nuclear factor ${\kappa}B\;(NF{\kappa}B)$ was significantly suppressed by $\beta$-glucan treatment with an $IC_{50}$ of $220\;{\mu}g/mL$ in a dose-dependent manner. Finally, barley $\beta$-glucan ameliorates NO production and iNOS expression through the down-regulation of $NF{\kappa}B$ activity, which may be mediated by attenuated oxidative stress in RAW 264.7 macrophages.

Forsythiaside, a Constituent of the Fruits of Forsythia suspense, Ameliorates Scopolamine-Induced Memory Impairment in Mice

  • Kim, Sun-Ho;Kim, Dong-Hyun;Choi, Ji-Joung;Lee, Jong-Gu;Lee, Choong-Ho;Park, Se-Jin;Jung, Won-Yong;Park, Dong-Hyun;Ko, Kwang-Ho;Lee, Seung-Ho;Ryu, Jong-Hoon
    • Biomolecules & Therapeutics
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    • v.17 no.3
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    • pp.249-255
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    • 2009
  • Forsythiaside is a polyphenolic constituent of the fruits of Forsythia suspense Vahl which are widely used as anti-inflammatory herbal raw materials in traditional Chinese medicine. In the present study, the authors assessed the effects of forsythiaside on learning and memory impairments induced by scopolamine using a passive avoidance and the Morris water maze tests in mice. Drug-induced amnesia was induced by scopolamine treatment (1 mg/kg, i.p.). Forsythiaside (10 mg/kg, p.o) administration significantly prevented scopolamine-induced step-through latency reduction in the passive avoidance test and scopolamine-induced increased escape latency in the Morris water maze test (p<0.05). Moreover, in an ex-vivo study, forsythiaside treatment (10 mg/kg, p.o) significantly reduced the increase of thiobarbituric acid reactive substance levels induced by scopolamine (p<0.05). Taken together, the present study suggests that forsythiaside could be useful for the treatment of cognitive impairment, and that its beneficial effects are mediated, in part, by its antioxidative properties.

Effects of Ginkgo(Ginkgo biloba L.) Leaf Wastes during Drug Manufacturing Process as Potential Organic Resources on Paddy Rice Growth (제약폐기(製藥廢棄) 은행잎이 벼생육에 미치는 영향)

  • Seong, Ki-Seog;Kim, Bok-Jin;Kwon, Oh-Kyung;Choi, Du-Hoi
    • Korean Journal of Soil Science and Fertilizer
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    • v.30 no.4
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    • pp.341-344
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    • 1997
  • To check the possibility to use the pharmaceutical by product of ginkgo leaf for the improvement soil fertility, a pot experiment was conducted with paddy rice. There were three treatment; NPK alone, NPK+7000kg(air dry)/ha of ginkgo leaf waste and NPK+700 kg of water-washed ginkgo leaf waste (air dry)/ha. The result indicated that the application of ginkgo leaf waste severely retarded the growth of rice. Water washing did reduce the severity of retardation, but the water washed ginkgo leaf waste also retarded the growth of rice significantly. The result of this study suggested that ginkgo leaf waste may contain some growth inhibiting substance.

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Antibacterial Activity of HTI Isolated from Oriental Medicine, Hyungbangjihwang-tang (형방지황탕으로부터 분리된 HTI의 항균 활성)

  • Sung, Woo-Sang;Seu, Young-Bae;Lee, Dong-Gun
    • Microbiology and Biotechnology Letters
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    • v.36 no.1
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    • pp.82-85
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    • 2008
  • Hyungbangjihwang-Tang (HT), an Oriental herbal formula, has been known to play a role which helps to recover vigor of human in the Orient. In this study, antibacterial substance (HTI) was purified from the ethyl-acetate extracts of HT by using $SiO_2$ column chromatography and HPLC, and the antibacterial effects of HTI were investigated. By using the CLSI broth micro-dilution assay, the activity of HTI was evaluated against human pathogenic Gram-positive and Gram-negative bacterial strains including the clinical isolates of methicillin-resistant Staphylococcus aureus. The results demonstrated that HTI showed broad spectrum antibacterial activities against all bacterial strains tested. In conclusion, HTI is an interesting new molecule for its potential in anti-infective drug discovery and for future studies on activity-structure relationship through analysis of its chemical structure.

Prognostic Factors of Acute Poisoning in Elderly Patients (65세 이상 노인 약물 중독 환자의 예후 인자)

  • Kim, Ji-Yoon;Jung, Hyun-Min;Kim, Ji-Hye;Han, Seung-Baik;Kim, Jun-Sig;Paik, Jin-Hui
    • Journal of The Korean Society of Clinical Toxicology
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    • v.9 no.2
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    • pp.81-87
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    • 2011
  • Purpose: Incidents of suicide attempt and acute poisoning in the elderly population is rising. This study investigated the clinical nature of acute poisoning and differences between the survival and mortality groups in the elderly. Methods: We retrospectively investigated 325 patients with acute poisoning who visited the emergency department. Patients were divided into two groups, one survival and one death group. Information regarding patient sex, age, root cause of poisoning, time of year of poisoning, type of intoxicant, duration of time between intoxicant ingestion and arrival at the emergency department, total length of hospital stay, and any previous suicide attempts and subsequent hospitalization were collected. An initial Glasgow Coma Scale (GCS) and an initial and final Poison Severity Score (PSS) for each patient was calculated. Results: The survival rate for men was higher than for women in this study. The most common reason of drug intoxication was suicide, with accidental ingestion and substance abuse occurring in descending frequency. Seasonal factors were reflected in the data with the highest number of incidents occurring in spring and the lowest number in winter. Compared with the mortality group, the survival group had a lower initial PSS with a higher GCS. Conclusion: We conclude that being female, having suicide as a root cause, agrochemicals as an intoxicant, low initial Glasgow Coma Scale and high initial Poisoning Severity Score, are all associated with poor prognosis.

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Degradation of Bradykinin, a Cardioprotective Substance, during a Single Passage through Isolated Rat-Heart

  • Ahmad M.;Zeitlin I.J.;Parratt J.R.;Pitt A.R.
    • Archives of Pharmacal Research
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    • v.29 no.3
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    • pp.241-248
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    • 2006
  • Angiotensin converting enzyme (ACE) inhibitors have cardioprotective effects in different species including human. This cardioprotective effect is mainly due to the inhibition of bradykinin (BK) degradation rather than inhibition of the conversion of angiotensin I to angiotensir. II. Bradykinin, a nonapeptide, has been considered to be the potential target for various enzymes including ACE, neutral endopeptidase 24.11, carboxypeptidase M, carboxypeptidase N, proline aminopeptidase, endopeptidase 24.15, and meprin. In the present study, the coronary vascular beds of Sprague Dawley rat isolated hearts were perfused (single passage) with Krebs solution alone or with different concentrations of BK i.e. $2.75{\times}10^{-10},\;10^{-7},\;10^{-6}\;and\;10^{-5}M$ solution. Percent degradation of BK was determined by radioimmunoassay. The degradation products of BK after passing through the isolated rat-hearts were determined using RP-HPLC and mass spectroscopy. All the four doses of BK significantly decreased the perfusion pressure during their passage through the hearts. The percentage degradation of all four doses was decreased as the concentration of drug was increased, implying saturation of a fixed number of active sites involved in BK degradation. Bradykinin during a single passage through the hearts degraded to give [1-7]-BK as the major metabolite, and [1-8]-BK as a minor metabolite, detected on HPLC. Mass spectroscopy not only confirmed the presence of these two metabolites but also detected traces of [1-5]-BK and arginine. These findings showed that primarily ACE is the major cardiac enzyme involved in the degradation of bradykinin during a single passage through the coronary vascular of bed the healthy rat heart, while carboxypeptidase M may have a minor role.

The Differences of Clinical Aspects in Children and Adolescents Poisoning (소아 및 청소년 중독 환자에서 중독 양상의 차이)

  • Suh Joo-Hyun;Eo Eun-Kyung
    • Journal of The Korean Society of Clinical Toxicology
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    • v.4 no.1
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    • pp.17-24
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    • 2006
  • Objectives: To analyze the general characteristics and clinical differences of poisoning in children and adolescents and to take precautions of occasions. Methods: We retrospectively evaluated poisoning children and adolescents (less than 19 years) visiting to the emergency medical center of tertiary hospital in urban area. We collected demographic data, substance exposure data (materials, causes of poisoning and amount), and clinical outcome of poisoning for the past 2 years and 9 months. Results: 189 cases were reported of concerning poisoning in children and adolescents. The age groups were divided into four categories. (1) Infants group:<2 year, (2) Preschool age group: $2{\sim}5year$, (3) Children group: $6{\sim}12year$ and (4) Adolescents group: $13{\sim}18year$. The most vulnerable age group was the infants group. There were two-peaks of age distribution in poisoned patients on the whole. Various types of materials belonged to classes of druqs (56.6%). household products (34.4%) and industrial solvents (9.0%). On adolescents group, the frequency of drug poisoning was significantly high, in comparison with infants, preschool age, and children group (p=0.001). Most of the patient groups had been poisoned accidentally(73.5%), while most cases of adolescents poisoning had been intentional. 63% of the adolescents group had a suicidal purpose. Conclusion: The incidence of poisoning was most highly due to drugs. The cause of poisoning is most commonly accidental. while in adolescent group, intentional poisoning is mostly common. Special cares, like keeping children away from drugs, will be needed to prevent children poisoning, and psychiatric consultation and supportive cares can reduce the adolescents poisoning cases.

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