• Title/Summary/Keyword: Preclinical

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Applications of Genetically Modified Tools to Safety Assessment in Drug Development

  • Kay, Hee-Yeon;Wu, Hong-Min;Lee, Seo-In;Kim, Sang-Geon
    • Toxicological Research
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    • v.26 no.1
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    • pp.1-8
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    • 2010
  • The process of new drug development consists of several stages; after identifying potential candidate compounds, preclinical studies using animal models link the laboratory and human clinical trials. Among many steps in preclinical studies, toxicology and safety assessments contribute to identify potential adverse events and provide rationale for setting the initial doses in clinical trials. Gene modulation is one of the important tools of modern biology, and is commonly employed to examine the function of genes of interest. Advances in new drug development have been achieved by exploding information on target selection and validation using genetically modified animal models as well as those of cells. In this review, a recent trend of genetically modified methods is discussed with reference to safety assessments, and the exemplary applications of gene-modulating tools to the tests in new drug development were summarized.

Establishment of normal reference of radiological morphology of renal artery in mini-pigs by renal angiography

  • Lee, Won Jae;Kim, Ji Yeon;Park, Jae Hyung;Park, Lisa Soyeon
    • Korean Journal of Veterinary Research
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    • v.56 no.3
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    • pp.177-181
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    • 2016
  • Mini-pigs have been widely employed in preclinical studies to explore new therapeutic strategies for diseases of the human urinary system; however, the normal reference of the renal artery has not been clearly investigated in the mini-pig model. Therefore, we aimed to establish a normal reference of the radiological morphology of the renal artery in mini-pigs by renal angiography via catheterization of the carotid artery. The renal angiographies obtained from 15 mini-pigs were evaluated to determine the orifice from the aorta, facing direction, size and the number of branches of renal arteries. Cranio-laterally facing renal arteries with 2 distal branches were mainly observed in the renal artery of mini-pigs. Both sides of the renal artery presented symmetrical sizes; however, the right renal artery orifice from the aorta was located more cranially than the left counterpart. The results of this study will contribute to radiological diagnosis of the renal artery as well as preclinical studies of mini-pigs.

Dilution Reference Ranges by Predictive Value of Serum Level β-hCG in Early Pregnancy Viability (임신 초기 임신양상에 따른 혈청 β-hCG의 결과 예측에 의한 희석배수 참고치 설정)

  • Kim, Yoon Sik;Shin, Jang Yong;Seo, Yeong Mi;Yoo, Shin Soo
    • Korean Journal of Clinical Laboratory Science
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    • v.36 no.2
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    • pp.210-214
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    • 2004
  • This study was carried out to predict the value of serum ${\beta}$ subunit of humans chorionic gonadotropin(${\beta}$- hCG) in early pregnancy viability. This was performed among 85 women in vitro fertilization and embryo transfer(IVF-ET). The serum ${\beta}$-hCG levels were established for 30 normal singleton pregnancies, 10 twin and triplet pregnancies, 10 preclinical abortions, 10 clinical abortions, 20 biochemical abortions and 5 ectopic pregnancies. In comparison to normal singleton pregnancies, multiple pregnancies showed higher ${\beta}$-hCG. But clinical abortions, preclinical abortions and ectopic pregnancies showed lower ${\beta}$-hCG levels than singleton pregnancies. In conclusion, if we predict the value of serum ${\beta}$-hCG of variable early pregnancies and analyze it, we could predict the dilution protocol. Also, it can be useful in other ways.

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Gastroprotective Effect of Korean Rice-Wine (Yakju) (한국 전통약주의 위보호 효과)

  • Kim, Seung-Jin;Baek, Ji-Young;Park, Chan-Koo;Kim, Gye-Won
    • Korean Journal of Food Science and Technology
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    • v.36 no.5
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    • pp.818-822
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    • 2004
  • Gastroprotective effects of Korean rice-wine (Yakju) in two types of acute experimental gastric ulcer induced in rats and in mice were evaluated. Korean rice-wine were administered to 24-hr fasted rats 30 min before administration of 60% EtOH in 150 mM HCl or absolute ethanol. Korean rice-wine prevented formation of gastric ulcers induced by 60% EtOH in 150 mM HCl at oral doses of 250-1,000mg/kg and reduced gastric ulcers induced by absolute ethanol at oral doses of 62.5-1,000mg/kg, and inhibitory effect against 30% alcohol treatment for 7 days (twice/day). These results suggest Korean rice-wine have inhibitory effects on gastric lesion and ulceration.

The G115 standardized ginseng extract: an example for safety, efficacy, and quality of an herbal medicine

  • Bilia, Anna R.;Bergonzi, Maria C.
    • Journal of Ginseng Research
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    • v.44 no.2
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    • pp.179-193
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    • 2020
  • Ginseng products on the market show high variability in their composition and overall quality. This becomes a challenge for both consumers and health-care professionals who are in search of high-quality, reliable ginseng products that have a proven safety and efficacy profile. The botanical extract standardization is of crucial importance in this context as it determines the reproducibility of the quality of the product that is essential for the evaluation of effectiveness and safety. This review focuses on the well-characterized and standardized ginseng extract, G115, which represents an excellent example of an herbal drug preparation with constant safety and efficacy within the herbal medicinal products. Over the many decades, extensive preclinical and clinical research has been conducted to evaluate the efficacy and safety of G115. In vitro and in vivo studies of G115 have shown pharmacological effects on physical performance, cognitive function, metabolism, and the immune system. Furthermore, a significant number of G115 clinical studies, most of them double-blind placebo-controlled, have reinforced the findings of preclinical evidence and proved the efficacy of this extract on blood glucose and lipid regulation, chronic obstructive pulmonary disease, energy, physical performance, and immune and cognitive functions. Clinical trials and 50 years of presence on the market are proof of a good safety profile of G115.

Vascular Morphometric Changes During Tumor Growth and Chemotherapy in a Murine Mammary Tumor Model Using OCT Angiography: a Preliminary Study

  • Kim, Hoonsup;Eom, Tae Joong;Kim, Jae Gwan
    • Current Optics and Photonics
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    • v.3 no.1
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    • pp.54-65
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    • 2019
  • To develop a biomarker predicting tumor treatment efficacy is helpful to reduce time, medical expenditure, and efforts in oncology therapy. In clinics, microvessel density using immunohistochemistry has been proposed as an indicator that correlates with both tumor size and metastasis of cancer. In the preclinical study, we hypothesized that vascular morphometrics using optical coherence tomography angiography (OCTA) could be potential indicators to estimate the treatment efficacy of breast cancer. To verify this hypothesis, a 13762-MAT-B-III rat breast tumor was grown in a dorsal skinfold window chamber which was applied to a nude mouse, and the change in vascular morphology was longitudinally monitored during tumor growth and metronomic cyclophosphamide treatment. Based on the daily OCTA maximum intensity projection map, multiple vessel parameters (vessel skeleton density, vessel diameter index, fractal dimension, and lacunarity) were compared with the tumor size in no tumor, treated tumor, and untreated tumor cases. Although each case has only one animal, we found that the vessel skeleton density (VSD), vessel diameter index and fractal dimension (FD) tended to be positively correlated with tumor size while lacunarity showed a partially negative correlation. Moreover, we observed that the changes in the VSD and FD are prior to the morphological change of the tumor. This feasibility study would be helpful in evaluating the tumor vascular response to treatment in preclinical settings.

Magnetic Resonance-Guided Focused Ultrasound : Current Status and Future Perspectives in Thermal Ablation and Blood-Brain Barrier Opening

  • Lee, Eun Jung;Fomenko, Anton;Lozano, Andres M.
    • Journal of Korean Neurosurgical Society
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    • v.62 no.1
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    • pp.10-26
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    • 2019
  • Magnetic resonance-guided focused ultrasound (MRgFUS) is an emerging new technology with considerable potential to treat various neurological diseases. With refinement of ultrasound transducer technology and integration with magnetic resonance imaging guidance, transcranial sonication of precise cerebral targets has become a therapeutic option. Intensity is a key determinant of ultrasound effects. High-intensity focused ultrasound can produce targeted lesions via thermal ablation of tissue. MRgFUS-mediated stereotactic ablation is non-invasive, incision-free, and confers immediate therapeutic effects. Since the US Food and Drug Administration approval of MRgFUS in 2016 for unilateral thalamotomy in medication-refractory essential tremor, studies on novel indications such as Parkinson's disease, psychiatric disease, and brain tumors are underway. MRgFUS is also used in the context of blood-brain barrier (BBB) opening at low intensities, in combination with intravenously-administered microbubbles. Preclinical studies show that MRgFUS-mediated BBB opening safely enhances the delivery of targeted chemotherapeutic agents to the brain and improves tumor control as well as survival. In addition, BBB opening has been shown to activate the innate immune system in animal models of Alzheimer's disease. Amyloid plaque clearance and promotion of neurogenesis in these studies suggest that MRgFUS-mediated BBB opening may be a new paradigm for neurodegenerative disease treatment in the future. Here, we review the current status of preclinical and clinical trials of MRgFUS-mediated thermal ablation and BBB opening, described their mechanisms of action, and discuss future prospects.

Pathophysiology and protective approaches of gut injury in critical illness

  • Jung, Chang Yeon;Bae, Jung Min
    • Journal of Yeungnam Medical Science
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    • v.38 no.1
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    • pp.27-33
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    • 2021
  • The gut is a complex organ that has played an important role in digestion, absorption, endocrine functions, and immunity. The gut mucosal barriers consist of the immunologic barrier and nonimmunologic barrier. During critical illnesses, the gut is susceptible to injury due to the induction of intestinal hyperpermeability. Gut hyperpermeability and barrier dysfunction may lead to systemic inflammatory response syndrome. Additionally, gut microbiota are altered during critical illnesses. The etiology of such microbiome alterations in critical illnesses is multifactorial. The interaction or systemic host defense modulation between distant organs and the gut microbiome is increasingly studied in disease research. No treatment modality exists to significantly enhance the gut epithelial integrity, permeability, or mucus layer in critically ill patients. However, multiple helpful approaches including clinical and preclinical strategies exist. Enteral nutrition is associated with an increased mucosal barrier in animal and human studies. The trophic effects of enteral nutrition might help to maintain the intestinal physiology, prevent atrophy of gut villi, reduce intestinal permeability, and protect against ischemia-reperfusion injury. The microbiome approach such as the use of probiotics, fecal microbial transplantation, and selective decontamination of the digestive tract has been suggested. However, its evidence does not have a high quality. To promote rapid hypertrophy of the small bowel, various factors have been reported, including the epidermal growth factor, membrane permeant inhibitor of myosin light chain kinase, mucus surrogate, pharmacologic vagus nerve agonist, immune-enhancing diet, and glucagon-like peptide-2 as preclinical strategies. However, the evidence remains unclear.

Selection for preclinical study candidate through analysis of frequently used medications presented in Donguibogam Stroke chapter (『동의보감(東醫寶鑑)』 풍문(風門) 처방 및 구성 약재의 인용 빈도 분석을 통한 전임상 연구 후보 약재 선별)

  • Lim, Chiyeon;Lim, Sehyun;Lee, Byoungho;Cho, Suin
    • Herbal Formula Science
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    • v.30 no.3
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    • pp.165-174
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    • 2022
  • Objectives: Donguibogam has helped progress of Eastern medicine across Asia and almost all of Korean medicine doctors still use the book as a classic reference. In this study, the prescriptions used in the treatment of stroke in Donguibogam are analyzed and the results are to be used for our subsequent studies. Methods: The frequency of use of prescriptions and the frequency of combination of medicines were analyzed from 89 prescriptions used in the Stroke chapter of Donguibogam, and it was intended to derive a combination prescription and a monosyllabic medicine that can be effectively used in the treatment of stroke for preclinical studies. Results: Ganghwalyupung-tang (羌活愈風湯) was the most mentioned prescription among 89 prescriptions, and Glycyrrhizae Radix et Rhizoma, among 165 species of medicines used in the 89 prescriptions, mixed in 55 prescriptions. However, considering the ratio of frequently used medicines, Sagunja-tang (四君子湯) was the highest in terms of composition ratio. Conclusions: Through this study, Glycyrrhizae Radix et Rhizoma and Sagunja-tang were selected as materials for our subsequent studies.

A Review of Clinical and Preclinical Studies on the Therapeutic Potential of Black Seeds (Nigella sativa) in the Management of Polycystic Ovarian Syndrome (PCOS)

  • Rajkapoor Balasubramanian;Naina Mohamed Pakkir Maideen;Sudha Muthusamy;Mirunalini Gobinath
    • Journal of Pharmacopuncture
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    • v.26 no.1
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    • pp.1-9
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    • 2023
  • Objectives: Polycystic ovary syndrome (PCOS) is a condition that occurs frequently among women of reproductive age and is a polygenic, multifactorial, endocrine, and metabolic disorder. PCOS is becoming more common as a result of risk factors such as current lifestyle, overnutrition, and stress. The use of traditional herbal medicine is higher among the global population. Hence, this review article focuses on the potential of Nigella sativa to manage women with PCOS. Methods: A literature search was carried out using databases including Medline, Google Scholar, EBSCO, Embase, and Science Direct, as well as reference lists, to identify relevant publications that support the use of N. sativa in the management of women with PCOS. Results: Several clinical and preclinical studies have demonstrated that the major bioactive constituent of black seed (N. sativa), thymoquinone, has potential for managing women with PCOS. Moreover, N. sativa may help to manage oligomenorrhea and amenorrhea in women with PCOS through its anti-inflammatory and antioxidant properties. Conclusion: N. sativa has potential for use as a herbal medicine for managing women with PCOS as an integrative medicine along with traditional and modern medicine in conjunction with calorie restriction and regular exercise.