• 제목/요약/키워드: pharmacological therapy

검색결과 240건 처리시간 0.027초

Induction of Prostaglandin E2 by Porphyromonas gingivalis in Human Dental Pulp Cells

  • Kim, So-Hee;Paek, Yun-Woong;Kang, In-Chol
    • International Journal of Oral Biology
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    • 제42권4호
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    • pp.149-153
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    • 2017
  • Cyclooxygenase-2 (COX-2)-mediated prostaglandin $E_2$ ($PGE_2$) plays a key role in development and progression of inflammatory responses and Porphyromonas gingivalis is a common endodontic pathogen. In this study, we investigated induction of COX-2 and $PGE_2$ by P. gingivalis in human dental pulp cells (HDPCs). P. gingivalis increased expression of COX-2, but not that of COX-1. Increased levels of $PGE_2$ were released from P. gingivalis-infected HDPCs and this $PGE_2$ increase was blocked by celecoxib, a selective COX-2 inhibitor. P. gingivalis activated all three types of mitogen-activated protein kinases (MAPKs). P. gingivalis-induced activation of nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$) was demonstrated by the results of phosphorylation of $NF-{\kappa}B$ p65 and degradation of inhibitor of ${\kappa}B-{\alpha}$ ($I{\kappa}B-{\alpha}$). Pharmacological inhibition of each of the three types of MAPKs and $NF-{\kappa}B$ substantially attenuated P. gingivalis-induced $PGE_2$ production. These results suggest that P. gingivalis should promote endodontic inflammation by stimulating dental pulp cells to produce $PGE_2$.

Review on Molecular and Chemopreventive Potential of Nimbolide in Cancer

  • Elumalai, Perumal;Arunakaran, Jagadeesan
    • Genomics & Informatics
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    • 제12권4호
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    • pp.156-164
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    • 2014
  • Cancer is the most dreaded disease in human and also major health problem worldwide. Despite its high occurrence, the exact molecular mechanisms of the development and progression are not fully understood. The existing cancer therapy based on allopathic medicine is expensive, exhibits side effects; and may also alter the normal functioning of genes. Thus, a non-toxic and effective mode of treatment is needed to control cancer development and progression. Some medicinal plants offer a safe, effective and affordable remedy to control the cancer progression. Nimbolide, a limnoid derived from the neem (Azadirachta indica) leaves and flowers of neem, is widely used in traditional medical practices for treating various human diseases. Nimbolide exhibits several pharmacological effects among which its anticancer activity is the most promising. The previous studies carried out over the decades have shown that nimbolide inhibits cell proliferation and metastasis of cancer cells. This review highlights the current knowledge on the molecular targets that contribute to the observed anticancer activity of nimbolide related to induction of apoptosis and cell cycle arrest; and inhibition of signaling pathways related to cancer progression.

Alk3/Alk3b and Smad5 Mediate BMP Signaling during Lymphatic Development in Zebrafish

  • Kim, Jun-Dae;Kim, Jongmin
    • Molecules and Cells
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    • 제37권3호
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    • pp.270-274
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    • 2014
  • Lymphatic vessels are essential to regulate interstitial fluid homeostasis and diverse immune responses. A number of crucial factors, such as VEGFC, SOX18, PROX1, FOX2C, and GJC2, have been implicated in differentiation and/or maintenance of lymphatic endothelial cells (LECs). In humans, dysregulation of these genes is known to cause lymphedema, a debilitating condition which adversely impacts the quality of life of affected individuals. However, there are no currently available pharmacological treatments for lymphedema, necessitating identification of additional factors modulating lymphatic development and function which can be targeted for therapy. In this report, we investigate the function of genes associated with Bone Morphogenetic Protein (BMP) signaling in lymphatic development using zebrafish embryos. The knock-down of BMP type II receptors, Bmpr2a and Bmpr2b, and type I receptors, Alk3 and Alk3b, as well as SMAD5, an essential cellular mediator of BMP signaling, led to distinct lymphatic defects in developing zebrafish. Therefore, it appears that each constituent of the BMP signaling pathway may have a unique function during lymphatic development. Taken together, our data demonstrate that BMP signaling is essential for normal lymphatic vessel development in zebrafish.

Magnolol exerts anti-asthmatic effects by regulating Janus kinase-signal transduction and activation of transcription and Notch signaling pathways and modulating Th1/Th2/Th17 cytokines in ovalbumin-sensitized asthmatic mice

  • Huang, Qi;Han, Lele;Lv, Rong;Ling, Ling
    • The Korean Journal of Physiology and Pharmacology
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    • 제23권4호
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    • pp.251-261
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    • 2019
  • Allergic asthma, is a common chronic inflammatory disease of the airway presenting with airway hyperresponsiveness and airway remodelling. T helper cells-derived cytokines are critically associated with asthma pathogenesis. Janus kinase-signal transduction and activation of transcription (JAK/STAT) signaling is found to be involved in asthma. Magnolol is a plant-derived bioactive compound with several pharmacological effects. The study aimed to assess the effects of magnolol in ovalbumin (OVA)-induced asthmatic model. BALB/c mice were sensitized and challenged with OVA. Magnolol (12.5, 25, or 50 mg/kg body weight) was administered to separate groups of animals. Dexamethasone was used as the positive control. Cellular infiltration into the bronchoalveolar lavage fluid (BALF) were reduced on magnolol treatment. The levels of Th2 and Th17 cytokines were reduced with noticeably raised levels of interferon gamma. Lung function was improved effectively along with restoration of bronchial tissue architecture. OVA-specific immunoglobulin E levels in serum and BALF were decreased by magnolol. Magnolol reduced Th17 cell population and effectively modulated the JAK-STAT and Notch 1 signaling. The results suggest the promising use of magnolol in therapy for allergic asthma.

Bio-guided Isolation of Natural Iron Chelators from Mangifera indica Leaves and their Comparative Study to Desferal®

  • Suliman, Sara N.;ElNaggar, Mai H.;Elsbaey, Marwa;El-Gamil, Mohammed M.;Badria, Farid A.
    • Natural Product Sciences
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    • 제27권2호
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    • pp.78-85
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    • 2021
  • Through bio-guided isolation, two natural iron chelators were isolated from Mangifera indica L. leaves, identified as mangiferin (1) and iriflophenone-3-C-𝛽-D-glucoside (2). Their iron-chelating activity was compared to that of Desferal® using bipyridyl assay and EDTA as a standard. Mangiferin showed the highest activity with IC50 value of 0.385 mM (162.85 ㎍/mL). Furthermore, two combinations of mangiferin with Desferal® (M-D) and iriflophenone-3-C-𝛽-D-glucoside (M-I) were evaluated. The results showed that mangiferin potentiated the iron chelation activity of Desferal® about 46%, also that M-I combination is a promising candidate formula for iron chelation therapy. In addition, mangiferin and Desferal-iron complexes were prepared and characterized by IR, UV, and Mass spectra to compare their mode of chelation to iron. Their structural stability was studied by DFT calculations. Furthermore, they displayed increased ABTS antioxidant activity when bound to iron as compared to their free form, which enhances their pharmacological importance.

Pain in amyotrophic lateral sclerosis: a narrative review

  • Kwak, Soyoung
    • Journal of Yeungnam Medical Science
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    • 제39권3호
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    • pp.181-189
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    • 2022
  • Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative condition characterized by loss of motor neurons, resulting in motor weakness of the limbs and/or bulbar muscles. Pain is a prevalent but neglected symptom of ALS, and it has a significant negative impact on the quality of life of patients and their caregivers. This review outlines the epidemiology, clinical characteristics, underlying mechanisms, and management strategies of pain in ALS to improve clinical practice and patient outcomes related to pain. Pain is a prevalent symptom among patients with ALS, with a variable reported prevalence. It may occur at any stage of the disease and can involve any part of the body without a specific pattern. Primary pain includes neuropathic pain and pain from spasticity or cramps, while secondary pain is mainly nociceptive, occurring with the progression of muscle weakness and atrophy, prolonged immobility causing degenerative changes in joints and connective tissue, and long-term home mechanical ventilation. Prior to treatment, the exact patterns and causes of pain must first be identified, and the treatment should be tailored to each patient. Treatment options can be classified into pharmacological treatments, including nonsteroidal anti-inflammatory drugs, antiepileptic drugs, drugs for cramps or spasticity, and opioid; and nonpharmacological treatments, including positioning, splints, joint injections, and physical therapy. The development of standardized and specific assessment tools for pain-specific to ALS is required, as are further studies on treatments to reduce pain, diminish suffering, and improve the quality of life of patients with ALS.

조현병 환자를 위한 정신사회적 중재 (Psychosocial Intervention for Patients with Schizophrenia)

  • 김성완
    • 신경정신의학
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    • 제57권3호
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    • pp.235-243
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    • 2018
  • Treatment of schizophrenia has as its ultimate goals, the functional recovery of the patients and improvement of their quality of life. While antipsychotic medication is the fundamental method for treating schizophrenia, it has certain limitations in terms of treating the illness beyond its positive symptoms. Therefore, psychosocial intervention should be used in tandem with pharmacological methods in treating schizophrenia. The efficacy of several modes of psychosocial intervention for improving outcomes in schizophrenia is well attested. Approximately 10 modes of psychosocial intervention have been recommended based on existing evidence, including family intervention, cognitive behavioral therapy, supported employment, early intervention services, lifestyle intervention for physical health enhancement, treatment of comorbid substance abuse, assertive community treatment, cognitive remediation, social skills training, and peer support. Ideally, these interventions are offered to patients in combination with one another. Over the last decade, increased emphasis has been placed on early detection and intervention, with particular focus on long-term recovery. Early intervention with comprehensive psychosocial interventions should be enacted promptly from the initial detection of schizophrenia.

수면클리닉을 방문한 환자들의 불면증에 대한 인식조사 (Survey of Knowledge on Insomnia for Sleep Clinic Clients)

  • 소민아
    • 수면정신생리
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    • 제26권1호
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    • pp.23-32
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    • 2019
  • 목 적 : 본 연구의 목적은 수면장애로 수면클리닉에 내원하는 환자들을 대상으로 수면클리닉을 방문하게 된 이유, 찾게 된 경로, 수면클리닉을 찾게 되는 가장 흔한 증상이자 독립질환인 불면증에 대한 인식을 조사하고 그 의미를 해석하여 향후 수면장애의 치료와 환자교육에 도움이 되고자 하였다. 방 법 : 2018년 4월부터 10월 사이 6개월 간 국립정신건강센터의 수면클리닉을 방문한 외래환자들 중 만 19세 이상의 초진환자를 대상으로 자기보고식 설문을 진행하였다. 이때, 지적장애, 치매 등 심한 인지기능을 동반한 환자등을 배제하였고, 총 44명(남성 24명, 여성 20명)이 연구에 참석하였다. 설문지는 자체개발한 설문지로 수면클리닉을 방문한 이유, 수면클리닉을 알게 된 경로, 수면클리닉 방문 이전 수면질환의 치료력, 불면증의 인식에 대한 질문, 불면증의 치료에 대한 인식, 불면증의 동반질환(comorbodity)에 대한 지식을 묻는 질문으로 구성되었다. 결 과 : 연구에 참가한 대상자들은 총 44명으로 평균 연령은 $54.11{\pm}16.3$세로 남성은 24명(54.5%), 여성은 20명(45.5%)였으며, 40대 이상의 중장년층이 전체의 77.3%를 차지했고, 81.8%(36명)가 고졸이상의 학력을 갖추고 있었다. 환자들의 72.7%(32명)가 공존질환을 갖고 있었으며, 22.7%에서 고위험음주를 보였다. 수면클리닉에 내원한 이유는 잠들기 힘들고 중간에 자주 깸, 낮에 피곤하고 졸림, 불규칙한 수면시간, 악몽을 자주 꿈, 코골이와 수면 중 숨막힘 등의 순서였고, 93.2%에서 불면증을 인식하고 있었고, 가족 친지, 방송, 인터넷 등을 통해 본인이 불면증에 대한 지식을 얻게 되었다고 하였다. 불면증의 치료에 대해서는 70.5%가 약물치료를 떠올렸고, 이에 대한 정보는 인터넷과 의료진을 통해 주로 얻고 있었으며 불면증의 비약물학적인 치료방법에 대해 52.3%가 들어본 적이 없다고 하였다. 불면증의 치료선호도를 묻는 질문에 45.5%가 특별한 선호도 없이 의사의 권유대로 따르겠다고 하였고, 불면증의 공존질환 중 우울증, 신체질환, 알코올사용장애을 알고 있는지를 묻는 질문에 대해 각각 75%, 50%, 38.6%의 응답률을 보였다. 수면제 복용 시 의사의 지침을 준수해야 한다는 것에 대해서는 75%에서 알고 있었지만, 전체 응답자의 68.2%가 수면제 처방에 대해 걱정을 하고 있었고 이들 중 70%가 약물의존에 대해 걱정된다고 하였다. 결 론 : 내원자의 56.8%가 내원전 타의료기관에서 수면장애로 치료를 받고 왔음에도 불구하고, 불면증의 치료, 특히 비약물학적인 치료에 대한 잘 알고 있지 못했으며, 본인의 수면제 복용여부와 상관없이 수면제에 대해서는 약물의존에 대한 걱정을 많이 하고 있었으나 상대적으로 불면증과 공존질환으로서의 알코올 사용문제에 대해서는 간과하고 있었다. 향후 일선 일차의료담당자의 불면증치료에 대한 이해증진 및 표준화된 불면증치료안의 개발이 시급할 것으로 생각된다. 또한 알코올 사용장애에 대한 구체적인 평가가 초기 면담에서 반드시 필요하다고 하겠다.

방사선 모사 미생물 유래 리보솜 스트레스에 의한 대장암 스페로이드 구조 결함 유발 (Structural Disorganization of Intestinal Tumor Spheroid by Microbial Ribotoxins)

  • 김주일;김중곤;유미라;문유석
    • 한국미생물·생명공학회지
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    • 제47권1호
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    • pp.164-171
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    • 2019
  • 기존에는 방사선 요법은 효과에 비해 소화기 점막 궤양 등 부작용이 많다. 본 연구는 방사선의 작용을 모사하는 방사선 모사 미생물 유래 리보솜 스트레스 반응을 이용하여 방사선 치료의 한계를 대체할 기전적 방법을 모색하고자 한다. 암 치료의 평가를 위해서 대장암의 비균질적인 세포구성, 종양줄기세포 및 주위 미세환경 및 배양 기질 등의 상호작용을 고려할 수 있는 소화기암 스페로이드를 이용하였다. 대조군 대장암 스페로이드에 비해서 리보솜 스트레스하에서는 스페로이드 구조가 상대적으로 큰 군집을 형성하였다. 하지만 이는 구조 자체가 매우 섬긴 세포간 구성을 가진 스페로이드였으며 스페로이드 형성과정의 크기 수축은 대조군에 비해 매우 느리게 나타났다. 대조군은 강하게 뭉친 소규모 클러스트의 집합체가 최종적으로 스페로이드를 형성하여 물리적 손상을 받아도 단단한 소규모 클러스트는 유지되나 리보솜 스트레스 하에서는 물리적 손상에 의해 형태가 파손 후에는 스페로이드 형성이 거의 일어나지 않았다. 기전적으로 리보솜 스트레스 하에서 암세포의 군집하는 이동속도는 매우 느렸으며, 뭉치더라도 세포-세포간 접합부위가 상대적으로 적었다. 이 대장암 스페로이드를 이종 및 동종 이식을 통해 동물에서 증식 시 종양 조직 형성이 매우 억제되었으며, 형성이 되어도 세포-세포간 접합에 핵심단백질인 E-cadherin의 발현이 매우 감소 됨을 알 수 있었다. 결론적으로 방사선 모사 미생물 유래 리보솜 스트레스는 종양 스페로이드 세포 이동 및 접합을 저해하여 3차원 구조 형성 결함을 유발하였으며, 향후 방사선을 대체하여 약물적으로 방사선 항암효과를 구현하는 기반을 제공한다.

Saudi Experts Consensus on Diagnosis and Management of Pediatric Functional Constipation

  • Alshehri, Dhafer B.;Sindi, Haifa Hasan;AlMusalami, Ibrahim Mohamod;Rozi, Ibrahim Hosamuddin;Shagrani, Mohamed;Kamal, Naglaa M.;Alahmadi, Najat Saeid;Alfuraikh, Samia Saud;Vandenplas, Yvan
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • 제25권3호
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    • pp.163-179
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    • 2022
  • Although functional gastrointestinal disorders (FGIDs) are very common in pediatric patients, there is a scarcity of published epidemiologic data, characteristics, and management patterns from Saudi Arabia, which is the 2nd largest Arabic country in terms of area and the 6th largest Arabic country in terms of population, with 10% of its population aged <5 years. Functional constipation (FC) is an FGID that has shown a rising prevalence among Saudi infants and children in the last few years, which urges us to update our clinical practices. Nine pediatric consultants attended two advisory board meetings to discuss and address current challenges, provide solutions, and reach a Saudi national consensus for the management of pediatric constipation. The pediatric consultants agreed that pediatricians should pay attention to any alarming signs (red flags) found during history taking or physical examinations. They also agreed that the Rome IV criteria are the gold standard for the diagnosis of pediatric FC. Different therapeutic options are available for pediatric patients with FC. Dietary treatment is recommended for infants with constipation for up to six months of age. When non-pharmacological interventions fail to improve FC symptoms, pharmacological treatment with laxatives is indicated. First, the treatment is aimed at disimpaction to remove fecal masses. This is achieved by administering a high dose of oral polyethylene glycol (PEG) or lactulose for a few days. Subsequently, maintenance therapy with PEG should be initiated to prevent the re-accumulation of feces. In addition to PEG, several other options may be used, such as Mg-rich formulas or stimulant laxatives. However, rectal enemas and suppositories are usually reserved for cases that require acute pain relief. In contrast, infant formulas that contain prebiotics or probiotics have not been shown to be effective in infant constipation, while the use of partially hydrolyzed formula is inconclusive. These clinical practice recommendations are intended to be adopted by pediatricians and primary care physicians across Saudi Arabia.