• Title/Summary/Keyword: Autopsy

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Epileptogenic Properties of Balloon Cells in Cortical Tubers of Tuberous Sclerosis : Upregulation of Drug Resistance Proteins

  • Kang, Nam-Gu;Chang, Hong-Joen;Ok, Young-Cheol;Lee, Rae-Seop;Park, Seung-Kyu;Lim, Jun-Seob;Cho, Kyu-Yong;Kim, Hyung-Ihl;Kim, Jae-Hyoo;Oh, Hyun-Sik;Lee, Min-Cheol
    • Journal of Korean Neurosurgical Society
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    • v.41 no.6
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    • pp.397-402
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    • 2007
  • Objective : Balloon cells and dysplastic neurons are histopathological hallmarks of the cortical tubers of tuberous sclerosis complex [TSC] and focal cortical dysplasia [FCD] of the Taylor type. They are believed to be the epileptogenic substrate and cause therapeutic drug resistant epilepsy in man. P-glycoprotein [P-gp] is the product of multidrug resistance gene [MDR1], and it maintains intracellular drug concentration at a relatively low level. The authors investigated expression of P-gp in balloon cells and dysplastic neurons of cortical tubers in patients with TSC. Methods : An immunohistochemical study using the primary antibody for P-gp, as an indicative of drug resistance, was performed in the cortical tuber tissues in two patients of surgical resection for epilepsy and six autopsy cases. Results : Balloon cells of each lesion showed different intensity and number in P-gp immunopositivity. P-gp immunopositivity in balloon cells were 28.2%, and dysplastic neurons were 22.7%. These immunoreactivities were more prominent in balloon cells distributed in the subpial region than deeper region of the cortical tubers. Capillary endothelial cells within the cortical tubers also showed P-gp immunopositivity. Conclusion : In this study, the drug resistance protein P-glycoprotein in balloon cells and dysplastic neurons might explain medically refractory epilepsy in TSC.

Biomechanical Properties of the Cranial Dura Mater with Puncture Defects : An In Vitro Study

  • Aydin, Hasan Emre;Kizmazoglu, Ceren;Kaya, Ismail;Husemoglu, Bugra;Sozer, Gulden;Havitcioglu, Hasan;Arslantas, Ali
    • Journal of Korean Neurosurgical Society
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    • v.62 no.4
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    • pp.382-388
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    • 2019
  • Objective : The primary aim of this investigation was to explore the nature of dura mater biomechanics following the introduction of puncture defect(s). Methods : Twenty-eight dura mater specimens were collected during autopsy from the department of forensic medicine of the authors' institution. Specimens were divided randomly into one of four groups : group I (cranial dura mater; n=7), group II (cranial dura mater with one puncture defect; n=7); group III (cranial dura mater with two puncture defects; n=7), and group IV (cranial dura mater with three puncture defects; n=7). Results : The mean${\pm}$standard deviation tensile strengths of the dura mater were $8.35{\pm}3.16$, $8.22{\pm}3.32$, $7.13{\pm}1.77$, and $6.94{\pm}1.93MPa$ for groups I, II, III, and IV, respectively. There was no statistical difference between all groups. A single, two or more punctures of the dura mater using a 20-gauge Quincke needle did not affect cranial dura tensile strength. Conclusion : This biomechanical study may contribute to the future development of artificial dura mater substitutes and medical needles that have a lower negative impact on the biomechanical properties of dura mater.

Single Oral Dose Toxicity Test and Four Weeks Repeated Oral Dose Determination Test of Oplopanax elatus (Nakai) Nakai Hydrothermal Extract Powder in Sprague-Dawley Rats (Sprague-Dawley 랫드를 이용한 땃두릅나무 열수추출물 분말의 단회 경구투여 독성시험 및 4주 반복 경구투여 용량 결정 시험)

  • Yoo, Nam Ho;Kwon, Yongsoo;Chun, Hyeon Soo;An, Kyu Sup;Kim, Hye Jin;Ryu, Hyeon Yeol;Lee, So Min;Song, Kyung Seuk;Park, Byung Jun;Kim, Myong Jo
    • Korean Journal of Pharmacognosy
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    • v.50 no.3
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    • pp.205-218
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    • 2019
  • This study was conducted to investigate the toxicity symptoms and approximate lethal dose (ALD) of Oplopanax elatus (Nakai) Nakai hydrothermal extract powder by single oral dose toxicity and 4 weeks of repeated oral dose determination. The Sprague-Dawley (SD) male and female rats were treated with 1,250 (low- dosage group), 2,500 (medium- dosage group) and 5,000 (high- dosage group) mg/kg. In the single oral dose toxicity test, no dead animals and toxic symptoms were observed during the experiment. And there were no related with anomalies in normal weight changes and autopsy results. In the four-week repeated oral dose determination test, no death animals and toxicity symptoms were observed during the experiment, and there were no abnormal results in weight changes, feed and negative intake measurements. Results of eye examination, urinalysis, hematological values and serum biochemical values, gross findings and absolute organ were not of singularity. These result demonstrated that no toxic symptoms were observed by the test substance Oplopanax elatus (Nakai) Nakai hydrothermal extract powder under this test condition, and the non-toxic content is determined to be 5,000 mg/kg/day.

Anti-obesity effects of Tenebrio molitor larvae powder in high-fat diet-induced obese mice

  • Park, Bo Mi;Lim, Hyung Ju;Lee, Bong Joo
    • Journal of Nutrition and Health
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    • v.54 no.4
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    • pp.342-354
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    • 2021
  • Purpose: Obesity is a serious public health issue for the modern society and is considered a chronic health hazard. There are many surgical and pharmacological approaches to treat obesity. However, various potentially hazardous side effects remain the biggest challenge. Therefore, diets based on foods derived from natural products have gained increasing attention compared to anti-obesity drugs. Recently, research on edible insects as a food source has been a topic of considerable interest in the scientific communities. This study examined the anti-obesity effects of ingesting an edible insect by feeding a high-fat diet (HFD)-induced obese mouse models with a diet containing Tenebrio molitor larvae powder (TMLP). Methods: Six-week-old female C57BL/6J mice were divided into 4 groups according to treatment: 100% normal diet (ND), 100% HFD (HFD), HFD 99% + TMLP 1% (TMLP), and HFD 97% + TMLP 3% (TMLP 3%). TMLP was added to the HFD for 6 weeks for the latter two groups. Results: Compared to the HFD group, mice in the TMLP group showed weight loss, and micro-computed tomographic imaging revealed that the volume of the adipose tissue in the abdominal area also showed significant reduction. After an autopsy, the fat weight was found to be significantly reduced in the TMLP group compared to the HFD group. In addition, the degree of fat cell deposition in the liver tissue and the size of the adipocytes significantly decreased in the TMLP group. Reverse transcription polymerase chain reaction analysis for the mRNA expression of adipogenesis-related genes namely CCAAT-enhancer-binding proteins (C/EBP-β, C/EBP-δ), and fatty acid-binding protein 4 (FABP4) showed that the expression levels of these genes were significantly reduced in the TMLP group compared to the HFD group. Serum leptin level also decreased significantly in the TMLP group in the comparison with the HFD group. In addition, total cholesterol, triglyceride, and glucose levels in mouse serum also decreased in the TMLP group. Conclusion: Taken together, our results showed that TMLP effectively inhibited adipocyte growth and reduced body weight in obese mice.

Evaluation of Acute Toxicity of Pomace Schisandra chinensis Extracts Using SD-rats (SD-rats를 이용한 오미자박 추출물의 급성경구독성 평가)

  • Seokho, Kim;Bo Ra, Yoo;Young-Suk, Kim;Jong-Min, Lim;Bon-Hwa, Ku;Kyeong Tae, Kwak;Byeong Yeob, Jeon
    • Herbal Formula Science
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    • v.30 no.4
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    • pp.281-291
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    • 2022
  • Objectives : In this study, acute oral toxicity test of pomace Schisandra chinensis extracts was conducted in order to up-cycling to a high value-added industry using by-products discarded in the production process of Schisandra chinensis products and active ingredients such as dibenzocyclooctadiene lignans in Schisandra chinensis. Methods : Pomace Schisandra chinensis extracts were orally administered to SD-rats(female, n=3) without a control group according to the 'OECD guidelines'. After, mortality and clinical signs were observed, and the deceased animals were subjected to an autopsy. In addition, acute oral toxicity test was sequentially performed in step I (300 mg/kg), step II(300 mg/kg), step III(2,000 mg/kg), and step IV(2,000 mg/kg) according to the mortality. Results : There were no abnormalities caused by pomace Schisandra chinensis extracts in step I and step II. However, one animal each died in step III and step IV. In addition, clinical signs(salivation, decrease in food intake, prone position, decrease of locomotor activity, loss of locomotor activity, convulsion, hypothermia, lacrimation, staining around mouth, soiled perineal region, reddish urine, chromaturia, decrease of fecal volume, lying on side, blackish stool, no stool, compound-colored stool, refusal to feed, excitement, hypersensitivity, rigidity, dorsal position, etc.) were observed. But, no clinical signs were observed from 5th day, and experiment animals recovered completely. Conclusions : As a result of this study, pomace Schisandra chinensis extracts may exhibit acute toxicity at concentrations of 2,000 to 5,000 mg/kg, and the GHS classification was designated as 'Category 5'.

Homozygous Missense Epithelial Cell Adhesion Molecule Variant in a Patient with Congenital Tufting Enteropathy and Literature Review

  • Guvenoglu, Merve;Simsek-Kiper, Pelin Ozlem;Kosukcu, Can;Taskiran, Ekim Z.;Saltik-Temizel, Inci Nur;Gucer, Safak;Utine, Eda;Boduroglu, Koray
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.25 no.6
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    • pp.441-452
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    • 2022
  • Congenital diarrheal disorders (CDDs) with genetic etiology are uncommon hereditary intestinal diseases characterized by chronic, life-threatening, intractable watery diarrhea that starts in infancy. CDDs can be mechanistically divided into osmotic and secretory diarrhea. Congenital tufting enteropathy (CTE), also known as intestinal epithelial dysplasia, is a type of secretory CDD. CTE is a rare autosomal recessive enteropathy that presents with intractable neonatal-onset diarrhea, intestinal failure, severe malnutrition, and parenteral nutrition dependence. Villous atrophy of the intestinal epithelium, crypt hyperplasia, and irregularity of surface enterocytes are the specific pathological findings of CTE. The small intestine and occasionally the colonic mucosa include focal epithelial tufts. In 2008, Sivagnanam et al. discovered that mutations in the epithelial cell adhesion molecule (EpCAM, MIM# 185535) were the genetic cause of CTE (MIM# 613217). More than a hundred mutations have been reported to date. Furthermore, mutations in the serine peptidase inhibitor Kunitz type 2 (SPINT2, MIM# 605124) have been linked to syndromic CTE. In this study, we report the case of a 17-month-old male infant with congenital diarrhea. Despite extensive etiological workup, no etiology could be established before admission to our center. The patient died 15 hours after being admitted to our center in a metabolically decompensated state, probably due to a delay in admission and diagnosis. Molecular autopsy with exome sequencing revealed a previously reported homozygous missense variant, c.757G>A, in EpCAM, which was confirmed by histopathological examination.

Assessment of acute inhalation toxicity of citric acid and sodium hypochlorite in rats

  • Jinhee Kim;Chul-Min Park;Su Hyun Choi;Mi Jin Yang;Ju-Yeon Lee;Byung-Suk Jeon;Hyun-Ok Ku;Min-Seok Kim
    • Journal of Veterinary Science
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    • v.24 no.2
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    • pp.22.1-22.12
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    • 2023
  • Background: Citric acid (CA) and sodium hypochlorite (NaOCl) have been used to disinfect animals to protect them against avian influenza and foot-and-mouth disease. Objectives: We performed a good laboratory practice (GLP)-compliant animal toxicity study to assess the acute toxic effects of CA and NaOCl aerosol exposure in Sprague-Dawley rats. Methods: Groups of five rats per sex were exposed for 4 h to four concentrations of the two chemicals, i.e., 0.00, 0.22, 0.67, and 2.00 mg/L, using a nose-only exposure. After a single exposure to the chemicals, clinical signs, body weight, and mortality was observed during the observation period. On day 15, an autopsy, and then gross findings, and histopathological analysis were performed. Results: After exposure to CA and NaOCl, body weight loss was observed but recovered. Two males died in the CA 2.00 mg/L group and, two males and one female died in the 2.00 mg/L NaOCl group. In the gross findings and histopathological analysis, discoloration of the lungs was observed in the CA exposed group and inflammatory lesions with discoloration of the lungs were observed in the NaOCl exposed group. These results suggest that the lethal concentration 50 (LC50) of CA is 1.73390 mg/L for males and > 1.70 mg/L for females. For NaOCl, the LC50 was 2.22222 mg/L for males and 2.39456 mg/L for females. Conclusions: The Globally Harmonized System is category 4 for both CA and NaOCl. In this study, the LC50 results were obtained through a GLP-based acute inhalation toxicity assessment. These results provide useful data to reset safety standards for CA and NaOCl use.

Large-scale purification and single-dose oral-toxicity study of human thioredoxin and epidermal growth factor introduced into two different genetically modified soybean varieties

  • Jung-Ho, Park
    • Korean Journal of Agricultural Science
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    • v.48 no.4
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    • pp.1003-1013
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    • 2021
  • Thioredoxin (TRX) protein is an antioxidant responsible for reducing other proteins by exchanging cysteine thiol-disulfide and is also known for its anti-allergic and anti-aging properties. On the other hand, epidermal growth factor (EGF) is an important material used in the cosmetics industry and an essential protein necessary for dermal wound healing facilitated by the proliferation and migration of keratinocytes. EGF also assists in the formation of granulation tissues and stimulates the motility of fibroblasts. Hence, genetically modified soybeans were developed to overexpress these industrially important proteins for mass production. A single-dose oral-toxicity-based study was conducted to evaluate the potential toxic effects of TRX and EGF proteins, as safety assessments are necessary for the commercial use of seed-specific protein-expressing transgenic soybeans. To achieve this rationale, TRX and EGF proteins were mass purified from recombinant E. coli. The single-dose oral-toxicity tests of the TRX and EGF proteins were carried out in six-week old male and female Institute of Cancer Research (ICR) mice. The initial evaluation of the single-dose TRF and EGF treatments was based on monitoring the toxicity signatures and mortality rates among the mice, and the resultant mortality rates did not show any specific clinical symptoms related to the proteins. Furthermore, no significant differences were observed in the weights between the treatment and control groups of male and female ICR mice. After 14 days of treatment, no differences were observed in the autopsy reports between the various treatment and control groups. These results suggest that the minimum lethal dose of TRX and EGF proteins is higher than the allowed 2,000 mg·kg-1 limit.

Characteristics of Patients who Died by Suicide in a Community Mental Health Center (정신건강센터 등록 회원 자살사망자 특성)

  • Nah, Gihoi;Choi, Seunggi;Kim, Honey;Lee, Ju-Yeon;Kim, Jae-Min;Shin, Il-Seon;Yoon, Jin-Sang;Kim, Sung-Wan
    • Korean Journal of Schizophrenia Research
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    • v.20 no.2
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    • pp.55-60
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    • 2017
  • Objectives : Severe mental illness is a major risk factor for suicide. This study aimed to identify characteristics of patients who died by suicide among subjects who had been received service from a community mental health center. Methods : We searched individuals who had committed suicide in Gwangju Bukgu Community Mental Health Center since 2006. Sociodemographic and clinical data were gathered from medical records and their case managers and they were compared with those of general members in the center. Characteristics of schizophrenia patients who died by suicide were particularly summarized. Results : Twelve person committed suicide between 2006 and 2016. The characteristics of those who died by suicide were male (67%), diagnosis of schizophrenia (75%), aged below 50 (83%), unemployed (92%), past history of psychiatric hospitalization (100%), recent admission within 3 months (67%), past history of suicidal attempt (78%), family history of schizophrenia (58%), poor adherence to medication (58%), and use of daily rehabilitation program (42%). Ten out of twelve (83%) showed warning sign for suicide. All identified method of suicide in patients with schizophrenia was jumping from high building. Many patients with schizophrenia, who committed suicide, suffered from comorbid depressive symptoms (67%) and auditory hallucination (78%). Conclusion : Case managers should pay attention to and carefully manage individuals who showed suicidal warning, particularly with risk factors for suicide, such as unemployment, admission state or recent discharge from psychiatric hospital, poor adherence to medication, family history of schizophrenia, and a history of suicidal attempt.

Single-Dose Toxicity Study of Intramuscular Neuralgia-Pharmacopuncture Injection in Rats

  • Ji Hye Hwang
    • Journal of Pharmacopuncture
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    • v.26 no.4
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    • pp.348-356
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    • 2023
  • Objectives: Neuralgia-pharmacopuncture (NP) was recently developed as a water-soluble type of pharmacopuncture inspired by CS (care special pain)-pharmacopuncture. I aimed to evaluate the toxic response and approximate lethal dose of when NP when administered intramuscularly to Sprague Dawley rats. Methods: The experimental group was divided into the NP test substance group and the saline control group and administered at a dose of 1.0 mL/animal to the posterior thigh muscles on both sides using a 1 mL syringe; each group consisted of five males and five females. Each rat was monitored for clinical signs and changes in body weight for 14 days after a single intramuscular injection. After completing observation, necropsy findings and localized tolerance at the injection site were assessed via gross necropsy and histopathological examination. Results: No deaths occurred in the NP or control group, regardless of sex. During the observation period, no changes (such as general symptoms, weight change, or visual observation results at the time of autopsy) were judged to be due to the test substance. Histopathological examination showed no changes at the administration site judged to be caused by the test substance in either the male or female test substance administration groups. In addition, mononuclear cell infiltration of the outer membrane of the femoris muscle at the administration site was observed at the same frequency and extent in the control and NP groups, and was judged to be caused by physical stimulation by the injection needle; therefore, it had no toxicological significance. Conclusion: Based on the above results, the approximate lethal dose for a single intramuscular administration of the test substance NP in Sprague-Dawley rats was judged to be > 1.0 mL/animal, and there were no findings that were judged to be due to the test substance at the administration site.