• Title/Summary/Keyword: Drug-associated

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Metformin ameliorates olanzapine-induced disturbances in POMC neuron number, axonal projection, and hypothalamic leptin resistance

  • Kim, Jaedeok;Lee, Nayoung;Suh, Sang Bum;Jang, Sooyeon;Kim, Saeha;Kim, Dong-Gyu;Park, Jong Kook;Lee, Keun-Wook;Choi, Soo Young;Lee, Chan Hee
    • BMB Reports
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    • v.55 no.6
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    • pp.293-298
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    • 2022
  • Antipsychotics have been widely accepted as a treatment of choice for psychiatric illnesses such as schizophrenia. While atypical antipsychotics such as aripiprazole are not associated with obesity and diabetes, olanzapine is still widely used based on the anticipation that it is more effective in treating severe schizophrenia than aripiprazole, despite its metabolic side effects. To address metabolic problems, metformin is widely prescribed. Hypothalamic proopiomelanocortin (POMC) neurons have been identified as the main regulator of metabolism and energy expenditure. Although the relation between POMC neurons and metabolic disorders is well established, little is known about the effects of olanzapine and metformin on hypothalamic POMC neurons. In the present study, we investigated the effect of olanzapine and metformin on the hypothalamic POMC neurons in female mice. Olanzapine administration for 5 days significantly decreased Pomc mRNA expression, POMC neuron numbers, POMC projections, and induced leptin resistance before the onset of obesity. It was also observed that coadministration of metformin with olanzapine not only increased POMC neuron numbers and projections but also improved the leptin response of POMC neurons in the olanzapine-treated female mice. These findings suggest that olanzapine-induced hypothalamic POMC neuron abnormality and leptin resistance, which can be ameliorated by metformin administration, are the possible causes of subsequent hyperphagia.

Effects of Pahs and Pcbs and Their Toxic Metabolites on Inhibition of Gjic and Cell Proliferation in Rat Liver Epithelial Wb-F344 Cells

  • Miroslav, Machala;Jan, Vondracek;Katerina, Chramostova;Lenka, Sindlerova;Pavel, Krcmar;Martina, Pliskova;Katerina, Pencikova;Brad, Upham
    • Environmental Mutagens and Carcinogens
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    • v.23 no.2
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    • pp.56-62
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    • 2003
  • The liver progenitor cells could form a potential target cell population fore both tumor-initiating and -promoting chemicals. Induction of drug-metabolizing and antioxidant enzymes, including AhR-dependent CYP1A1, NQO-1 and AKR1C9, was detected in the rat liver epithelial WB-F344 "stem-like" cells. Additionally, WB-F344 cells express a functional, wild-type form of p53 protein, a biomarker of genotoxic events, and connexin 43, a basic structural unit of gap junctions forming an important type of intercellular communication. In this cellular model, two complementary assays have been established for detection of the modes of action associated with tumor promotion: inhibition of gap junctional intercellular communication (GJIC) and proliferative activity in confluent cells. We found that the PAHs and PCBs, which are AhR agonists, released WB-F344 cells from contact inhibition, increasing both DNA synthesis and cell numbers. Genotoxic effects of some PAHs that lead to apoptosis and cell cycle delay might interfere with the proliferative activity of PAHs. Contrary to that, the nongenotoxic low-molecular-weight PAHs and non-dioxin-like PCB congeners, abundant in the environment, did not significantly affect cell cycle and cell proliferation; however both groups of compounds inhibited GJIC in WB-F344 cells. The release from contact inhibiton by a mechanism that possibly involves the AhR activation, inhibition of GJIC and genotoxic events induced by environmental contaminants are three important modes of action that could play an important role in carcinogenic effects of toxic compounds. The relative potencies to inhibit GJIC, to induce AhR-mediated activity, and to release cells from contact inhibition were determined for a large series of PAHs and PCBs and their metabolites. In vitro bioassays based on detection of events on cellular level (deregulation of GJIC and/or proliferation) or determination of receptor-mediated activities in both ?$stem-like^{\circ}{\times}$ and hepatocyte-like liver cellular models are valuable tools for detection of modes of action of polyaromatic hydrocarbons. They may serve, together with concentration data, as a first step in their risk assessment.

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Prediction of pathogen positive-culture results in acute poisoning patients with suspected aspiration (흡인이 의심되는 급성 중독환자에서 병원균 양성 배양 결과의 예측)

  • Baek Sungha;Park Sungwook
    • Journal of The Korean Society of Clinical Toxicology
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    • v.20 no.2
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    • pp.75-81
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    • 2022
  • Purpose: This study sought to compare the characteristics of patients with pathogen-positive and negative cultures, and to investigate factors predicting pathogen-positive culture results in patients of acute poisoning with suspected aspiration. Methods: Consecutive patients with acute poisoning admitted to an intensive care unit between January 2016 and December 2018 were retrospectively studied. Respiratory specimens were collected from the enrolled patients at the time of the suspected aspiration. We compared the characteristics of patients with pathogen-positive and negative culture results and analyzed the causative pathogens. Results: Among the 526 patients, 325 showed no clinical features that could be attributed to aspiration, and 201 patients had clinical features suggestive of aspiration. Of these, 113 patients had pathogen-positive culture, 61 were negative, and the specimens of 27 patients contained poor-quality sputum. In univariate analysis, patients with a positive culture showed a longer time to culture from ingestion (p=0.01), faster heart rate (p=0.01), and higher partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2) (p=0.02) than patients with negative culture. Multivariate analysis demonstrated that PaO2/FiO2 (adjusted odd ratio, 1.005; 95% confidence interval [CI], 1.002-1.008; p=0.005) was a significant risk factor for pathogen-positive culture. The area under the receiver operating characteristic curve of PaO2/FiO2 was 0.591 (95% CI, 0.510-0.669, p=0.05). Gram-negative pathogens (GNPs) were predominant and at least one GNP was observed in 84 (73.3%) patients among those with pathogen positive culture. Conclusion: We failed to find any clinical factors associated with positive culture results. Antibiotics that cover GNPs could be considered when deciding the initial antibiotic regimen at the time of suspected aspiration.

circRNA circSnx12 confers Cisplatin chemoresistance to ovarian cancer by inhibiting ferroptosis through a miR-194-5p/SLC7A11 axis

  • Kaiyun Qin;Fenghua Zhang;Hongxia Wang;Na Wang;Hongbing Qiu;Xinzhuan Jia;Shan Gong;Zhengmao Zhang
    • BMB Reports
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    • v.56 no.3
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    • pp.184-189
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    • 2023
  • Ovarian cancer (OC) is the most common gynecological malignancy worldwide, and chemoresistance occurs in most patients, resulting in treatment failure. A better understanding of the molecular processes underlying drug resistance is crucial for development of efficient therapies to improve OC patient outcomes. Circular RNAs (circRNAs) and ferroptosis play crucial roles in tumorigenesis and resistance to chemotherapy. However, little is known about the role(s) of circRNAs in regulating ferroptosis in OC. To gain insights into cisplatin resistance in OC, we studied the ferroptosis-associated circRNA circSnx12. We evaluated circSnx12 expression in OC cell lines and tissues that were susceptible or resistant to cisplatin using quantitative real-time PCR. We also conducted in vitro and in vivo assays examining the function and mechanism of lnc-LBCSs. Knockdown of circSnx12 rendered cisplatin-resistant OC cells more sensitive to cisplatin in vitro and in vivo by activating ferroptosis, which was at least partially abolished by downregulation of miR-194-5p. Molecular mechanics studies indicate that circSnx12 can be a molecular sponge of miR-194-5p, which targets SLC7A11. According to our findings, circSnx12 ameliorates cisplatin resistance by blocking ferroptosis via a miR-194-5p/SLC7A11 pathway. CircARNT2 may thus serve as an effective therapeutic target for overcoming cisplatin resistance in OC.

Mid- to long-term success rate and functional outcomes of acromioclavicular injections in patients with acromioclavicular osteoarthritis

  • Nienke Miedema;Inger Sierevelt;Tjarco Dirk Willem Alta;Roderick Jan Maximiliaan Vossen;Arthur van Noort
    • Clinics in Shoulder and Elbow
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    • v.26 no.2
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    • pp.175-181
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    • 2023
  • Background: Acromioclavicular (AC) osteoarthritis (OA) is a frequent pathology of the shoulder in elderly patients. Drug injection plays an important role in treatment of AC OA. Literature has demonstrated excellent short-term results regarding shoulder function and pain. However, mid- to long-term results are lacking. The aim of this study was to assess the efficacy of a single intra-articular AC injection in patients with AC OA and to identify predictive factors for success. Methods: A retrospective study was performed to analyze success rate, shoulder function, and pain perception after a single intra-articular injection in patients with AC OA. Success was defined as the absence of reinterventions such as additional injection or surgery. Outcome measures were 1-year success rate and clinical outcome scores of Numeric Rating Scale (NRS) for pain, Oxford Shoulder Score, and Subjective Shoulder Value. Results: Ninety-eight patients participated in this study. At a median final follow-up of 0.8 years (interquartile range, 0-6), 57 of these patients (58%) had undergone a reintervention. The 1-year success rate was 47% (95% confidence interval, 37%-57%), with NRS at rest as the sole factor significantly associated with success. Thirty patients not requiring reintervention reported significant improvement from baseline for all reported outcome measures at final follow-up. Conclusions: AC injections offer a 1-year success rate of 47%. The AC injection produces good mid- to long-term clinical outcomes regarding shoulder function, quality of life, and pain perception in one-third of patients. Further research is essential to analyze mid- to long-term outcomes of AC injections.

Evaluation of Antioxidant and Anticancer Activity of Guarana and Graviola in Human Colon Cancer (과라나와 그라비올라가 인체 대장암에 미치는 항산화 및 항암효과에 대한 연구)

  • Lee, Myeong-Seon
    • Journal of Korea Entertainment Industry Association
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    • v.13 no.1
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    • pp.217-223
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    • 2019
  • Colon cancer is the most common form of cancer diagnosis in worldwide. There are growing interests in the health benefits associated with consumption of fruits and vegetables, especially for the prevention of cancer, cardiovascular or other chronic diseases. The objective of the present study was to investigate the antioxidant and anticancer activities of natural product, guarana(GR) and graviola(GV) in human colon carcinoma HCT-116 cells. MTT assay, flow cytometry analysis were employed to investigate the anticancer mechanism and DPPH assay was determined to the antioxidant activity to scavenge free radicals in extract of these. All two extracts showed significantly antioxidant activity at 50mg/ml of concentration. GR and GV reduced HCT-116 cell proliferation in a dose dependent manner. Specially GR treatment(96.65±3.71) also significantly increased the sub-G1 population more than GV(79.58±2.87) treatment in HCT-116 at the concentration of 10mg/ml, as shown by flow cytometry assay. Statistical analyses revealed GR and GV exhibited significantly high (P < 0.05) cytotoxicity in HCT-116. These findings indicate that GN and GV may serve as novel therapeutic agents for colon cancer treatment and future leads for drug development.

A Case Report of Stevens-Johnson Syndrome with Intraoral Lesions (구강 증상을 동반한 Stevens-Johnson 증후군의 임상 증례)

  • Kim, K.A.;Jang, S.Y.;Ryu, S.S.;Byun, Y.H.;Lee, J.M.;Lee, C.H.;Kee, W.C.;Choi, J.K.
    • Journal of Oral Medicine and Pain
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    • v.22 no.1
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    • pp.23-29
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    • 1997
  • A 49 years old male patient was referred from the Department of Medicine, KNUH for the management of painful oral lesions. The patient had disability of food and drug intake due to multiple intraoral ulcers. Extraoral findings showed upper and lower lip swelling, crust formation on the lips. The lesions were diagnosed as Stevens-Johnson syndrome based on clinical and hematologic findings. The patient was treated with saline irrigation and pulsed Nd:YAG laser irradiation. After 5 daily treatment, the lesions decreased in size and severity, and the patient became more comfortable for food intake and speeching. It was suggested from the results of this clinical trial that a pulsed Nd:YAG laser therapy would be helpful for the symptoms associated with Stevens-Johnson syndrome.

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EFFICACY OF HAMῡL OF MARHAME DAKHILYUN AND ROGHANE SAUSAN IN CERVICITIS (ILTIHAB-E-UNUQ-UL- REHAM)- AN OPEN OBSERVATIONAL CLINICAL STUDY

  • HUMA;PROF WAJEEHA BEGUM;KOUSER FATHIMA FIRDOSE
    • CELLMED
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    • v.13 no.6
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    • pp.4.1-4.10
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    • 2023
  • Background and objective: Cervicitis are an inflammatory condition of the cervix. This may be acute, chronic, active & specific or non-specific, which may cause various sign & symptoms. Abnormal vaginal discharge, lower abdominal pain, lower backache, post coital bleeding. If not treated timely it causes various complications viz PID, infertility, endometritis, ectopic pregnancy etc. Hence it has been decided to conduct a clinical trial for its management. Method: This study was an open observational study. The entire patients were allocated by considering the criteria of inclusion & exclusion. Marhame dakhilyun with roghane sausan is given 10 mg as ḥamūl at bed time, after menses for 21 days. All the patients were assessed by primary outcome of abnormal vaginal discharge, lower abdominal pain, lower backache, post coital bleeding & secondary outcomes of vaginal symptoms scale score (VSS) which score the vaginal discharge with QOL in cervicitis patients and vaginal analogue scale (VAS) for pain. Result: In this present study, marked improvement is observed in cervicitis. The mean ± SD of vaginal discharge before & after treatment is 2.57±0.050, 0.33±0.48 respectively which is highly significant with p value of<0.0001**. VSS score before & after treatment is 21.27±6.12, 7.47±2.48 respectively with p<0.0001** which is highly significant. VAS score used for LAB & LPA before & after treatment is 6.63±1.09, 1.90±1.29 respectively with p<0.0001** which is highly significant. Interpretation & Conclusion: The study revealed that the formulation has been found effective in healing congestion, hypertrophied of the cervix and discharge and relieving the others associated symptoms of cervicitis. It is useful and provided immediate and effective treatment for cervicitis. Hence, the trial drug can be recommended for its management.

A Cohen syndrome patient whose muscle-relaxant effect may have been prolonged during general anesthesia: a case report

  • Ishikawa, Emi;Shibuya, Makiko;Kimura, Yukifumi;Kamekura, Nobuhito;Fujisawa, Toshiaki
    • Journal of Dental Anesthesia and Pain Medicine
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    • v.22 no.2
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    • pp.155-159
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    • 2022
  • Cohen syndrome is a rare genetic disorder associated with mutations in the VPS13B gene. Individuals with this disorder present with diverse clinical manifestations, including muscle hypotonia, intellectual disabilities, and typical facial characteristics, such as prominent upper central incisors and micrognathia. General anesthesia was administered to a 23-year-old man with Cohen syndrome. Although we observed prominent upper central incisors, an overjet of 10 mm, micrognathia, and thyromental distance of 4 cm, hypotonia was not observed in the patient. Intubation was rendered difficult when performing a direct laryngoscopy. However, smooth intubation was achieved using a video laryngoscope. The patient's train of four (TOF) count remained zero close to 60 min after rocuronium administration, suggesting that the drug's muscle-relaxant effect may have been prolonged. A TOF ratio of 0.79 was confirmed 130 min after rocuronium administration, and a TOF ratio of 1.0 was confirmed after administration of 150 mg of sugammadex. The patient's respiration remained stable after extubation, and no recurarization of muscle relaxation was observed. As demonstrated in this case report, it is important to closely monitor recovery from muscle relaxation and prepare multiple techniques for airway management in general anesthesia management of patients with Cohen syndrome.

Long-Term Management of Seizures after Surgical Treatment of Supratentorial Cavernous Malformations : A Retrospective Single Centre Study

  • Dziedzic, Tomasz A.;Koczyk, Kacper;Nowak, Arkadiusz;Maj, Edyta;Marchel, Andrzej
    • Journal of Korean Neurosurgical Society
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    • v.65 no.3
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    • pp.415-421
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    • 2022
  • Objective : Seizure recurrence after the first-ever seizure in patients with a supratentorial cerebral cavernous malformation (CCM) is almost certain, so the diagnosis and treatment of epilepsy is justified. The optimal method of management of these patients is still a matter of debate. The aim of our study was to identify factors associated with postoperative seizure control and assess the surgical morbidity rate. Methods : We retrospectively analysed 45 consecutive patients with a supratentorial CCM and symptomatic epilepsy in a single centre. Pre- and postoperative epidemiological data, seizure-related patient histories, neuroimaging results, surgery details and outcomes were obtained from hospital medical records. Seizure outcomes were assessed at least 12 months after surgery. Results : Thirty-five patients (77.8%) were seizure free at the long-term follow-up (Engel class I); six (13,3%) had rare, nocturnal seizures (Engel class II); and four (8.9%) showed meaningful improvement (Engel class III). In 15 patients (33%) in the Engel I group; it was possible to discontinue antiepileptic medication. Although there was not statistical significance, our results suggest that patients can benefit from early surgery. No deaths occurred in our study, and mild postoperative neurologic deficits were observed in two patients (4%) at the long-term follow-up. Conclusion : Surgical resection of CCMs should be considered in all patients with a supratentorial malformation and epilepsy due to the favourable surgical results in terms of the epileptic seizure control rate and low postoperative morbidity risk, despite the use of different predictors for the seizure outcome.