• Title/Summary/Keyword: pathological findings

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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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    • 제25권6호
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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.

Microbiota, co-metabolites, and network pharmacology reveal the alteration of the ginsenoside fraction on inflammatory bowel disease

  • Dandan Wang;Mingkun Guo;Xiangyan Li;Daqing Zhao;Mingxing Wang
    • Journal of Ginseng Research
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    • 제47권1호
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    • pp.54-64
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    • 2023
  • Background: Panax ginseng Meyer (P. ginseng) is a traditional natural/herbal medicine. The amelioration on inflammatory bowel disease (IBD) activity rely mainly on its main active ingredients that are referred to as ginsenosides. However, the current literature on gut microbiota, gut microbiota-host co-metabolites, and systems pharmacology has no studies investigating the effects of ginsenoside on IBD. Methods: The present study was aimed to investigate the role of ginsenosides and the possible underlying mechanisms in the treatment of IBD in an acetic acid-induced rat model by integrating metagenomics, metabolomics, and complex biological networks analysis. In the study ten ginsenosides in the ginsenoside fraction (GS) were identified using Q-Orbitrap LC-MS. Results: The results demonstrated the improvement effect of GS on IBD and the regulation effect of ginsenosides on gut microbiota and its co-metabolites. It was revealed that 7 endogenous metabolites, including acetic acid, butyric acid, citric acid, tryptophan, histidine, alanine, and glutathione, could be utilized as significant biomarkers of GS in the treatment of IBD. Furthermore, the biological network studies revealed EGFR, STAT3, and AKT1, which belong mainly to the glycolysis and pentose phosphate pathways, as the potential targets for GS for intervening in IBD. Conclusion: These findings indicated that the combination of genomics, metabolomics, and biological network analysis could assist in elucidating the possible mechanism underlying the role of ginsenosides in alleviating inflammatory bowel disease and thereby reveal the pathological process of ginsenosides in IBD treatment through the regulation of the disordered host-flora co-metabolism pathway.

Chronic Toxicity of a Combined Preparation of Ticlopidine and Ginkgo Biloba Extract (EGb 761) Orally Administered to Rats for 13 Consecutive Weeks

  • Kim, Sang K.;Kim, Sung Y.;Yoon, Mi Y.;Oh, Soo J.;Kim, Hye S.;Lee, Ja Y.;Kang, Sung A.;Lee, Kyung H.;Kim, Young C.
    • Toxicological Research
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    • 제16권4호
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    • pp.293-301
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    • 2000
  • Toxicity of a combined preparation of ticlopidine and ginkgo biloba extract (EGb 761) in a ratio of 10: 4 was examined in male and female Sprague-Dawley rats. Rats were treated with the test substance intragastrically at a dose of 0 mg/kg, 17 mg/kg, 52 mg/kg or 156 mg/kg for 91 consecutive days. No death or abnormal clinical sign was observed throughout the administration period. There was no difference in body weight gain, food intake or water consumption among different dose groups. Test sub-stance-related differences were not observed in urinalysis. In hematological results mean corpuscular hemoglobin (MCH) of low and high dose male group was increased. Prothrombin time of medium and high dose female group was decreased. A significant increase in serum total cholesterol was observed in both sexes of rats treated with a daily dose of 156 mg/kg, but all the other values obtained in serum chemistry appeared to be within normal ranges. A dose dependent increase in the relative liver and kidney weights was observed in both male and female rats. There were no gross pathological findings at terminal sacrifice. Microscopic histopathological examination did not show any lesion associated with administration of the test substance. The results suggest that under the conditions employed in this study no observable effect level (NOEL) of the test substance be greater than 17 mg/kg/day, but less than 52 mg/kg/day.

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Therapeutic effects of selective p300 histone acetyl-transferase inhibitor on liver fibrosis

  • Hyunsik Kim;Soo-Yeon Park;Soo Yeon Lee;Jae-Hwan Kwon;Seunghee Byun;Mi Jeong Kim;Sungryul Yu;Jung-Yoon Yoo;Ho-Geun Yoon
    • BMB Reports
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    • 제56권2호
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    • pp.114-119
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    • 2023
  • Liver fibrosis is caused by chronic liver damage and results in the aberrant accumulation of extracellular matrix during disease progression. Despite the identification of the HAT enzyme p300 as a major factor for liver fibrosis, the development of therapeutic agents targeting the regulation of p300 has not been reported. We validated a novel p300 inhibitor (A6) on the improvement of liver fibrosis using two mouse models, mice on a choline-deficient high-fat diet and thioacetamide-treated mice. We demonstrated that pathological hall-marks of liver fibrosis were significantly diminished by A6 treatment through Masson's trichrome and Sirius red staining on liver tissue and found that A6 treatment reduced the expression of matricellular protein genes. We further showed that A6 treatment improved liver fibrosis by reducing the stability of p300 protein via disruption of p300 binding to AKT. Our findings suggest that targeting p300 through the specific inhibitor A6 has potential as a major therapeutic avenue for treating liver fibrosis.

Inflammatory response to Trichomonas vaginalis in the pathogenesis of prostatitis and benign prostatic hyperplasia

  • Ik-Hwan Han;Jung-Hyun Kim;Jae-Sook Ryu
    • Parasites, Hosts and Diseases
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    • 제61권1호
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    • pp.2-14
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    • 2023
  • Trichomonas vaginalis is a flagellated protozoan that causes trichomoniasis, a common nonviral sexually transmitted infection. T. vaginalis infection is asymptomatic in most infected men but can lead to chronic infection. The inflammatory response to chronic T. vaginalis infection may contribute to prostatic diseases, such as prostatitis and benign prostatic hyperplasia (BPH); however, studies on the relationship between T. vaginalis infection and prostate diseases are scarce. In this review, we discuss evidence from our studies on the involvement of T. vaginalis in the pathogenesis of prostate diseases, such as prostatitis and BPH. Studies of prostatitis have demonstrated that the attachment of T. vaginalis trophozoite to prostate epithelial cells (PECs) induces inflammatory cytokine production and inflammatory cell migration, leading to prostatitis. T. vaginalis also causes pathological changes, such as inflammatory cell infiltration, acinar changes, interstitial fibrosis, and mast cell infiltration, in prostate tissues of infected rats. Thus, T. vaginalis is considered an infectious agent that triggers prostatitis. Meanwhile, studies of prostatic hyperplasia revealed that mast cells activated by T. vaginalis-infected prostate cells secreted inflammatory mediators, such as β-hexosaminidase and tryptase, which promoted proliferation of prostate stromal cell (PSC). Moreover, interleukin-6 produced by proliferating PSCs induced the multiplication of BPH-1 epithelial cells as a result of stromal-epithelial interaction, suggesting that the proliferation of T. vaginalis-infected prostate cells can be induced through crosstalk with mast cells. These collective findings suggest that T. vaginalis contributes to the progression of prostatitis and prostatic hyperplasia by creating an inflammatory microenvironment involving PECs and PSCs.

6-Shogaol, an Active Ingredient of Ginger, Improves Intestinal and Brain Abnormalities in Proteus Mirabilis-Induced Parkinson's Disease Mouse Model

  • Eugene Huh;Jin Gyu Choi;Yujin Choi;In Gyoung Ju;Dongjin Noh;Dong-yun Shin;Dong Hyun Kim;Hi-Joon Park;Myung Sook Oh
    • Biomolecules & Therapeutics
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    • 제31권4호
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    • pp.417-424
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    • 2023
  • Parkinson's disease (PD) which has various pathological mechanisms, recently, it is attracting attention to the mechanism via microbiome-gut-brain axis. 6-Shogaol, a representative compound of ginger, have been known for improving PD phenotypes by reducing neuroinflammatory responses. In the present study, we investigated whether 6-shogaol and ginger attenuate degeneration induced by Proteus mirabilis (P. mirabilis) on the intestine and brain, simultaneously. C57BL/6J mice received P. mirabilis for 5 days. Ginger (300 mg/kg) and 6-shogaol (10 mg/kg) were treated by gavage feeding for 22 days including the period of P. mirabilis treatment. Results showed that 6-shogaol and ginger improved motor dysfunction and dopaminergic neuronal death induced by P. mirabilis treatment. In addition, they suppressed P. mirabilis-induced intestinal barrier disruption, pro-inflammatory signals such as toll-like receptor and TNF-α, and intestinal α-synuclein aggregation. Moreover, ginger and 6-shogaol significantly inhibited neuroinflammation and α-synuclein in the brain. Taken together, 6-shogaol and ginger have the potential to ameliorate PD-like motor behavior and degeneration of dopaminergic neurons induced by P. mirabilis in mice. Here, these findings are meaningful in that they provide the first experimental evidence that 6-shogaol might attenuate PD via regulating gut-brain axis.

소비자의 저장강박이 제품유형(쾌락적/실용적)에 따른 구매의도에 미치는 영향 (The Effect of Compulsive Hoarding of Consumers on Product Type(Hedonic/Utilitarian) Purchase Intention)

  • 김나예;배정호
    • 아태비즈니스연구
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    • 제14권1호
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    • pp.247-263
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    • 2023
  • Purpose - The purpose of this study is to examine the influence of the compulsive hoarding behavior of consumers on the intention to purchase hedonic and utilitarian types of products. Design/methodology/approach - The online and offline survey was conducted and a total of 210 domestic data were collected. Simple and multiple regression analysis and ANOVA were conducted to analyze the data. Findings - First, the consumers'compulsive hoarding behavior had a significantly positive influence on the purchase intention. According to the analysis results of the sub-factors, however, only 'Difficulty Discarding' had a significant influence on the purchase intention, while 'Clutter' and 'Acquisition' did not. Second, as the results of identifying the moderating effect by product type in the purchase intention in accordance with the consumers'compulsive hoarding behavior, their compulsive hoarding behavior had a significant influence on only the intention to purchase hedonic products but not on the intention to purchase utilitarian ones. Similarly, the results of analyzing the sub-factors showed that only'Difficulty Discarding' significantly influenced the intention to purchase hedonic types of products, but 'Clutter' and 'Acquisition' were not significantly influential to both the hedonic and utilitarian types of products. Research implications or Originality - First, this study is meaningful in that it expanded the research discussion on compulsive hoarding behavior by conducting empirical research on this behavior in the general public, which is unlike the previous studies that focused on only severe pathological compulsive hoarding behavior. Second, it identified that the consumers'compulsive hoarding behavior could cause purchase behaviors that were different depending on the type of product by searching the purchase intention with divided types of products (hedonic and utilitarian).

Ruminal impaction with an indigestible foreign body in long-tailed goral (Naemorhedus caudatus)

  • Sangjin Ahn;Woojin Shin;Yujin Han;Sohwon Bae;Chea-Un Cho;Sooyoung Choi;Yeonsu Oh;Jong-Taek Kim
    • 한국동물위생학회지
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    • 제46권2호
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    • pp.161-165
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    • 2023
  • A 6-year-old female long-tailed goral (Naemorhedus caudatus, goral) was admitted to the Gangwon wildlife medical rescue center due to severe starvation and hypothermia. The goral displayed clinical signs of severe weight loss, dehydration, lethargy, regurgitation, hypothermia, and bloating, with blood tests showing a decrease in albumin, calcium, glucose, and sodium. Supportive care was given through heating, oxygen supply, and fluid therapy, but the goral's condition worsened, and the goral died three days after admission. Radiographic and computed tomography scans revealed the presence of an indigestible foreign body (IFB) in the rumen, which was confirmed during the necropsy. The cause of goral's death was identified as chronic rumen impaction caused by the IFB (a ball of string), with other pathological findings including bloating, the presence of serous ascites, and congestion of digestive organs. Blood biochemical changes, clinical signs, and veterinary medical imaging diagnosis can be helpful in diagnosing ruminal impaction. This case report can provide valuable information for the diagnosis and treatment of ruminal impaction caused by IFB in endangered gorals, which may include rumenotomy or other surgical procedures.

Clinical and radiological characteristics of odontomas: A retrospective study of 90 cases

  • Dung Kim Nguyen;Duong Van Huynh
    • Imaging Science in Dentistry
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    • 제53권2호
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    • pp.117-126
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    • 2023
  • Purpose: Odontomas represent a common clinical entity among odontogenic tumors, but are not well-addressed in the Vietnamese population. The present study aimed to determine the clinical and preclinical characteristics of odontomas and associated factors in the Vietnamese population. Materials and Methods: This retrospective study retrieved data from histopathological diagnoses from 2 central hospitals of Odonto-Stomatology in Ho Chi Minh City, Vietnam during 2004-2017. The odontomas were classified as complex (CxOD) or compound (CpOD) subtypes. The epidemiological, clinical, and radiological characteristics of the odontomas, stratified by subtype and sex, were obtained and analyzed. Results: Ninety cases, consisting of 46 CxODs and 44 CpODs, were included. The average age of patients was 32.4 (±20.2) years. The patients with CxOD were older than those with CpOD (P<0.05). Clinically, 67% of patients showed an intraoral bone expansion. Approximately 60% of patients with CxOD exhibited a painful symptom, about 3-fold more than those with CpOD (P<0.05), whereas almost all patients with CpOD exhibited perturbations of dentition, unlike those with CxOD (P<0.05). Radiologically, CxOD was characterized by a larger dimension than CpOD in both sexes (P<0.05), and CpOD induced complications in adjacent teeth more often than CxOD (P<0.05). The development of odontoma with advancing age differed significantly in odontoma subtypes related to their pathological origins, and between the sexes, resulting from different physiological states. Conclusion: The findings of this study highlight the value of clinical and radiological features of odontomas and their associated factors for the early diagnosis and adequate treatment of younger patients.

ICR 마우스를 이용한 초석잠, 석창포 단독추출물 및 복합추출물의 단회경구투여 독성시험 (Single Dose Oral Toxicity Test of Water Extracts of Stachys sieboldii and Acorus gramineus, and their Mixture in ICR Mice)

  • 안은정;신수영;이승영;이창민;최경민;정진우
    • 한국자원식물학회:학술대회논문집
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    • 한국자원식물학회 2021년도 춘계학술대회
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    • pp.59-59
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    • 2021
  • Stachys sieboldii Miq. (SSM) and Acorus gramineus Soland. (AGS) have been used as traditional medicines for thousands of years in parts of Asia, including Korea, China, and Japan. Recent researches on SSM and AGS have documented a wide spectrum of therapeutic properties, including anti-inflammatory, anti-oxidative, neurodegenerative disease effects. However, the toxicity and safety of SSM and AGS, and their mixture (medicinal herber mixture, MHMIX) were not confirmed. Therefore, this study was performed to evaluate the acute toxicity and safety of SSM, AGS and MHMIX. SSM, AGS and MHMIX were orally administered at a dose of 5,000 mg/kg in ICR mice. Animals were monitored for the mortality and changes in the body weight, clinical signs and gross observation during the 14 days after dosing, upon necropsy. We also measured parameters of organ weight, clinical chemistry, and hematology. No dead and no clinical signs were found during the experiment period after administration of a single oral dose of SSM, AGS and MHMIX. There were no adverse effects on clinical signs, body weight, or organ weight and no gross pathological findings in any treatment group. Therefore, LD50 value of SSM, AGS and MHMIX may be over 5,000 mg/kg and it may have no side toxic effect to ICR mice. The results on the single-dose toxicity of SSM, AGS and MHMIX indicate that it is not possible to reach oral dose levels related to death or dose levels with any harmful side effects.

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