A case of acute poisoning caused by oral administration of large dose hexazinone / 中华劳动卫生职业病杂志

Hexazinone is a post-emergence herbicide/arboricides, and its acute poisoning has rarely been reported. Hexazinone is low-toxic to humans, but mass intake of hexazinone would still lead to organ impairment. This article analyzes a case of acute hexazinone poisoning from the poisoning treatment center of our hospital, and summarizes the symptoms and treatment effects of hexazinone poisoning, which is aimed at improving the comprehension, diagnosis and treatment of the disease.

Anticholinesterase activity of ß-carboline-1, 3, 5-triazine hybrids

Abstract The ß-carboline-1,3,5-triazine hydrochlorides 8-13 were evaluated in vitro against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The analysed compounds were selective to BuChE, with IC50 values in the range from 1.0-18.8 µM being obtained. The N-{2-[(4,6-dihydrazinyl-1,3,5-triazin-2-yl)amino]ethyl}-1-phenyl-ß-carboline-3-carboxamide (12) was the most potent compound and kinetic studies indicate that it acts as a competitive inhibitor of BuChE. Molecular docking studies show that 12 strongly interacts with the residues of His438 (residue of the catalytic triad) and Trp82 (residue of catalytic anionic site), confirming that this compound competes with the same binding site of the butyrylthiocholine

Clinicopathological features and prognosis of gastrointestinal stromal tumors with KIT/PDGFRA gene "homozygous mutation": a multicenter retrospective cohort study / 中华胃肠外科杂志

Objective: To investigate the clinicopathological features of gastrointestinal stromal tumor (GIST) with KIT/PDGFRA "homozygous mutation", the efficacy of targeted therapy and the prognosis. Methods: A retrospective cohort study and propensity score matching were used. "Homozygous mutation" was defined as the detection of KIT/PDGFRA gene status of GIST by Sanger sequencing, which showed that there was only mutant gene sequence in the sequencing map, lack of wild-type sequence or the peak height of mutant gene sequence was much higher than that of wild-type gene sequence (> 3 times). "Heterozygous mutation" was defined as the mutant gene sequences coexisted with wild type gene sequences, and the peak height was similar (3 times or less). The clinicopathological data and follow-up information of 92 GIST patients with KIT/PDGFRA "homozygous mutation" were collected from 4 hospitals in Shanghai from January 2008 to May 2021 (Renji Hospital, Shanghai Jiaotong University School of Medicine: 70 cases; Zhongshan Hospital, Fudan University: 14 cases; Changhai Hospital, Naval Military Medical University: 6 cases and Ruijin Hospital, Shanghai Jiaotong University School of Medicine: 2 cases). Patients with perioperative death, other malignancies, and incomplete clinicopathological information were excluded. The clinicopathological features of the patients and the efficacy of targeted drug therapy were observed and analyzed. The efficacy was evaluated using Choi criteria, which were divided into complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). In addition, a total of 230 patients with high-risk GIST with "heterozygous mutation" in exon 11 of KIT gene and 117 patients with recurrent or metastatic GIST with "heterozygous mutation" in exon 11 of KIT gene were included. The propensity score matching method was used to match GIST patients with "heterozygous" and "homozygous" mutations in exon 11 of KIT gene (1∶1) for survival analysis. The disease-free survival (DFS) between two groups of high-risk GIST patients who underwent complete surgical resection were compared. And progression-free survival (PFS) in patients with recurrent or metastatic GIST were compared. Results: Of the 92 GIST cases with KIT/PDGFRA "homozygous mutation", 58 were males and 34 were females, with a median onset age of 62 (31-91) years. Primary GIST 83 cases. Primary high-risk GIST (53 cases), metastatic GIST (21 cases) and recurrent GIST (9 cases) accounted for 90.2% (83/92). There were 90 cases of KIT gene"homozygous mutation" (exon 11 for 88 cases, exon 13 for 1 case, exon 17 for 1 case), and 2 cases of PDGFRA gene "homozygous mutation" (exon 12 for 1 case, exon 18 for 1 case). The median follow-up time was 49 (8-181) months. Among the 61 cases of primary localized GIST undergoing complete surgical resection, 2 cases were intermediate-risk GIST, 5 cases were low-risk GIST, and 1 case was very low-risk GIST, of whom 1 case of intermediate-risk GIST received 1-year adjuvant imatinib mesylate (IM) therapy after operation, and no tumor recurrence developed during the follow-up period. The remaining 53 cases were high-risk GIST, and follow-up data were obtained from 50 cases, of whom 22 developed tumor recurrence during follow-up. Of 9 patients directly receiving neoadjuvant targeted therapy (IM or avapritinib), 5 had complete imaging follow-up data, and the evaluation of efficacy achieved PR. Of all the 92 GIST cases with KIT/PDGFRA "homozygous mutation", 50 (54.4%) had tumor metastasis or tumor recurrence or progression during follow-up, and 12 (13.0%) died of the tumor. Survival analysis combined with propensity score showed that in 100 cases of high-risk GISTs with complete resection, GISTs with "homozygous mutation" in exon 11 of KIT gene had shorter disease-free survival (DFS) than GISTs with "heterozygous mutation" in exon 11 of KIT gene (median DFS: 72 months vs. 148 months, P=0.015). In 60 cases of recurrent or metastatic GISTs with KIT gene exon 11 mutation, IM was used as the first-line treatment, and the progression-free survival (PFS) of GISTs with "homozygous mutation" was shorter compared to GISTs with "heterozygous mutation" (median PFS: 38 months vs. 69 months, P=0.044). The differences were statistically significant. Conclusions: "Homozygous mutation" in KIT/PDGFRA gene is associated with the progression of GIST. The corresponding targeted therapeutic drugs are still effective for GIST with KIT/PDGFRA gene "homozygous mutation". Compared with GIST patients with "heterozygous mutation" in KIT exon 11, GIST patients with "homozygous mutation" in KIT exon 11 are more likely to relapse after surgery and to develop resistance to IM. Therefore, it is still necessary to seek more effective treatment methods for this subset of cases.

The Antileukemia Activity of ZSTK474 on U937 Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the antileukemia activity of phosphatidylinositol-3 kinase (PI3K) inhibitor ZSTK474 on human leukemia cell line U937.@*METHODS@#MTT, soft agar assay, flow cytometric analysis and western blot were used to detect the effect of ZSTK474 on U937 cell proliferation, tumorigenicity, cell cycle, cell apoptosis and phosphorylation levels of the key factor of PI3K/AKT pathway. Chou-Talalay method was used to evaluate the combination of ZSTK474 with Cytarabine or Homoharringtonine.@*RESULTS@#PI3K inhibitor ZSTK474 could inhibit the proliferation and tumorigenicity of U937 cell, induce G@*CONCLUSION@#ZSTK474 can inhibit the pathway of PI3K/AKT, ZSTK474 alone or in combination with Homoharringtonine shows potential antileukemia activity on U937 cells.

Evaluation of the cytotoxic and genotoxic effects by melamine and cyanuric acid co-exposure in human embryonic kidney 293 cells

The melamine and cyanuric acid (CA) complex has been suggested to cause the toxic effects observed in melamine-contaminated food or milk. However, the cytotoxic and genotoxic effects of co-exposure to melamine and CA are not fully clear. Therefore, the cytotoxic effects of melamine and CA were first examined by co‐exposure in human kidney 293 cells using the MTT assay. During a 24-h period for the three concentrations tested (0.5, 1, and 5 mg/mL), neither melamine nor CA alone showed significant toxic effects on 293 cells at 0.5 mg/mL, while higher concentrations led to decreased in cell viability. However, co-exposure to several combinations of melamine and CA [100:1, 10:1, 1:10, and 1:100 (v:v), at a final concentration of 0.5 mg/mL] did cause cytotoxicity with higher levels of CA leading to higher cytotoxicity. By contrast, while neither melamine nor CA alone induced phosphorylated-H2AX (γH2AX) foci formation, melamine and CA at a 100:1 ratio induced γH2AX foci 24 h post-treatment. The alkaline comet assay also revealed the presence of DNA damage following melamine and CA co-exposure. In vivo assay also revealed the presence of melamine-CA complex in the kidney. These data indicated that the cytotoxic and genotoxic effects of melamine and CA co-exposure differ from those of melamine or CA alone.

Overexpression of autophagy-related gene 3 promotes autophagy and inhibits salinomycin-induced apoptosis in breast cancer MCF-7 cells / 南方医科大学学报

OBJECTIVE@#To study the effects of the overexpression of autophagy-related gene 3 (ATG3) on autophagy and salinomycin-induced apoptosis in breast cancer cells and explore the underlying mechanisms.@*METHODS@#We used the lentivirus approach to establish a breast cancer cell line with stable overexpression of ATG3. Western blotting, immunofluorescence staining and transmission electron microscopy were used to analyze the effect of ATG3 overexpression on autophagy in breast cancer MCF-7 cells. Using the AKT/mTOR agonists SC79 and MHY1485, we analyzed the effect of AKT/mTOR signal pathway activation on ATG3 overexpression-induced autophagy. Western blotting and flow cytometry were used to analyze the effect of autophagy on apoptosis of the ATG3-overexpressing cells treated with salinomycin and 3-MA (an autophagy inhibitor).@*RESULTS@#In ATG3-overexpressing MCF-7 cells, ATG3 overexpression obviously promoted autophagy, inhibited the AKT/mTOR signaling pathway, significantly weakened salinomycin-induced apoptosis ( < 0.01), caused significant reduction of the levels of the pro-apoptotic proteins cleaved-caspase 3 ( < 0.01) and Bax ( < 0.05), and enhanced the expression of the anti-apoptotic protein Bcl-2 ( < 0.05). The inhibition of autophagy obviously weakened the inhibitory effect of ATG3 overexpression on salinomycin-induced apoptosis.@*CONCLUSIONS@#ATG3 overexpression promotes autophagy possibly by inhibiting the AKT/mTOR signaling pathway to decrease salinomycin-induced apoptosis in MCF-7 cells, suggesting that autophagy induction might be one of the mechanisms of drug resistance in breast cancer cells.

Occupational Risk Factors for Prostate Cancer: A Meta-analysis

Prostate cancer is the second most common cancer in men worldwide. There are many occupational factors that have been suggested to cause prostate cancer. Our aim was to evaluate the evidence for causality by a literature review of occupational factors. We searched literature in Medline and SCOPUS from 1966 to June 30, 2015 to identify occupational risk factors for prostate cancer. The following risk factors were selected: farmers/agricultural workers, pesticides – whole group, and separately organophosphate and organochlorine pesticides, carbamates and triazines, cadmium, chromium, cutting fluids, acrylonitrile, rubber manufacturing, whole body vibration, shift work, flight personnel, ionizing radiation, and occupational physical activity. For each factor a literature search was performed and presented as meta-analysis of relative risk and heterogeneity (Q and I² index). A total of 168 original studies met the inclusion criteria with 90,688 prostate cancer cases. Significantly increased risks were observed for the following occupational exposures: pesticides (metaRR = 1.15, 95% confidence interval [CI] = 1.01–1.32; I² = 84%), and specifically group of organochlorine pesticides (meta relative risk [metaRR] = 1.08, 95% CI = 1.03–1.14; I² = 0%), chromium (metaRR = 1.19, 95% CI = 1.07–1.34; I² = 31%), shift work (metaRR = 1.25, 95% CI = 1.05–1.49; I² = 78%) and pilots (metaRR = 1.41, 95% CI = 1.02–1.94; I² = 63%) and occupational physical activity in cohort studies (metaRR = 0.87, 95% CI = 0.81–0.94; I² = 0%). The literature review supports a causal association for a few of the previously suggested factors.

Levetiracetam and lamotrigine effects as mono- and polytherapy on bone mineral density in epileptic patients / Efeitos do levetiracetam e lamotrigina, em mono e politerapia, na densidade mineral óssea de pacientes epilépticos

ABSTRACT The purpose of this study was to determine the effect of lamotrigine (LTG) and levetiracetam (LEV) as mono- and polytherapy on biochemical markers of bone turnover and bone mineral density in Egyptian adult patients with epilepsy. Methods Forty-eight patients were divided into four groups: two received monotherapy of either LTG or LEV, and the other two groups received polytherapy comprising (valproate [VPA] + LTG or VPA + LEV). Thirty matched healthy participants were included in the study. Participants completed a nutritional and physical activity questionnaire. Biochemical markers of bone and mineral metabolism and bone mineral density of the lumbar spine were measured at baseline and at six months. Results In the LEV monotherapy group, the bone formation markers showed a significant decrease in serum alkaline phosphatase and serum osteocalcin levels while the bone resorption marker showed a significant increase in urinary deoxypyridinoline levels. After six months of treatment, bone mineral density showed a significant decrease in all treated groups, while among monotherapy groups, this significant decrease was more prevalent in the LEV monotherapy group compared with the LTG monotherapy group. Furthermore, there was significant negative correlation between urinary deoxypyridinoline levels and bone mineral density in the LEV monotherapy group. Conclusion Using new generation antiepileptics, LEV monotherapies and polytherapy showed harmful effects on bone but LTG did not.

RESUMO O objetivo deste estudo foi determinar o efeito da lamotrigina (LTG) e levetiracetam (LEV) como mono e politerapia em marcadores bioquímicos de remodelação óssea e densidade mineral óssea em pacientes adultos egípcios com epilepsia. Métodos Quarenta e oito pacientes foram divididos em quatro grupos: dois grupos receberam monoterapia de LTG ou LEV e os outros dois grupos receberam politerapia (valproato [VPA] + LTG ou VPA + LEV). Trinta participantes saudáveis controle foram incluídos no estudo. Os participantes preencheram um questionário nutricional e de atividade física. Marcadores bioquímicos do metabolismo ósseo e mineral e densidade mineral óssea da coluna lombar foram medidos no início e aos seis meses. Resultados No grupo de monoterapia LEV, os marcadores de formação óssea mostraram uma diminuição significativa nos níveis séricos de fosfatase alcalina e osteocalcina sérica, enquanto o marcador de reabsorção óssea mostrou um aumento significativo nos níveis de desoxipiridinolina urinária. Após seis meses de tratamento, a densidade mineral óssea mostrou uma diminuição significativa em todos os grupos tratados, enquanto entre os grupos de monoterapia, esta diminuição significativa foi mais prevalente no grupo de monoterapia LEV em comparação com o grupo de monoterapia LTG. Além disso, houve correlação negativa significativa entre os níveis de desoxipiridinolina urinária e densidade mineral óssea no grupo de monoterapia LEV. Conclusão Utilizando antiepilépticos de nova geração, as monoterapias LEV e a politerapia mostraram efeitos prejudiciais no osso, mas a LTG não.

Triazine Compound as Copolymerized Antibacterial Agent in Adhesive Resins

Abstract The aim of this study was to formulate and evaluate an experimental adhesive resin with the addition of 1,3,5-triacryloylhexahydro-1,3,5-triazine at different concentrations. Experimental adhesive resins were obtained by mixing 50% wt bisphenol A glycol dimethacrylate (BisGMA), 25% wt triethylene glycol dimethacrylate (TEGDMA), 25% wt 2-hydroxyethyl methacrylate (HEMA) and photoinitiator system. The triazine compound was added in 1, 2.5 and 5% wt to a base adhesive resin and one group remained with no triazine as control group. The experimental adhesive resins were analyzed for antibacterial activity (n=3), degree of conversion (n=3) and softening in solvent (n=3). Data distribution was evaluated by Kolmogorov-Smirnov test, paired t test, one-way ANOVA and Tukey’s with a 0.05 level of significance. All groups with added triazine compound showed antibacterial activity against Streptococcus mutans (p<0.05). All groups achieved more than 70% degree of conversion, but there was no difference in this chemical property (p>0.05). The initial Knoop hardness was higher in 2.5 and 5% wt groups (p<0.05) and both groups present lower percentage variation of Knoop hardness after solvent degradation. The present study formulated an antibacterial adhesive resin with a non-releasing agent able to copolymerize with the comonomeric blend, improving the restorative material’s properties.

Resumo O objetivo desse estudo foi desenvolver e avaliar a adição de 1,3,5-triacryloylhexahydro-1,3,5-triazine a uma resina adesiva experimental em diferentes concentrações. Resinas adesivas experimentais foram obtidas a partir da mistura de 50% em peso de bisphenol A glycol dimethacrylate (BisGMA), 25% em peso de triethylene glycol dimethacrylate (TEGDMA), 25% em peso de hidroxietil metacrilato (HEMA) e sistema fotoiniciador. O composto de triazina foi adicionado em proporções de 1; 2,5 e 5% em peso a resina adesiva base e um grupo permaneceu sem a adição do composto de triazina como grupo controle. As resinas adesivas experimentais foram analisadas por atividade antibacteriana (n=3), grau de conversão (n=3) e degradação em solvente (n=3). A distribuição dos dados foi avaliada por teste de Kolmogorov-Smirnov, teste t pareado, ANOVA de uma via e Tukey, considerando nível de significância de 5%. Todos os grupos com adição de composto de triazina demonstraram atividade antibacteriana contra Streptococcus mutans (p<0,05). Todos os grupos atingiram mais de 70% de grau de conversão, mas não houve diferença estatística para essa propriedade química (p>0,05). A dureza Knoop inicial foi maior para os grupos com 2,5 e 5% de triazina (p<0,05) e ambos os grupos apresentaram menor variação percentual de dureza Knoop após degradação em solvente. No presente estudo, foi produzida uma resina adesiva antibacteriana com agente sem liberação para o meio, capaz de copolimerizar com a blenda comonomérica, melhorando as propriedades do material restaurador.

Identifying the incidence of rash, Stevens-Johnson syndrome and toxic epidermal necrolysis in patients taking lamotrigine: a systematic review of 122 randomized controlled trials

ABSTRACT Lamotrigine is an antiepileptic drug used for the treatment of epilepsy, bipolar disorder and numerous off-label uses. The development of rash significantly affects its use. The most concerning of these adverse reactions is Stevens-Johnson syndrome/toxic epidermal necrolysis. We performed a systematic review of randomized controlled trials using lamotrigine as a monotherapy to quantify the incidence of cutaneous reactions, particularly Stevens-Johnson syndrome/toxic epidermal necrolysis. Of a total of 4,364 papers regarding lamotrigine, 122 studies met our inclusion and exclusion criteria. In total, 18,698 patients were included with 1,570 (8.3%) of patients experiencing an adverse dermatologic reaction. The incidence of Stevens-Johnson syndrome/toxic epidermal necrolysis was 0.04%.

A case report on catamenial epilepsy / Philippine Journal of Obstetrics and Gynecology

A case of a 17-year-old nulligravid with onset of seizure episodes since menarcheis reported. She was diagnosed with Seizure Disorder treated with Phenobarbital and was seizure free for 2 years. Two years prior to consult, seizure recurrences were noted to coincide with menstruation, hence, was diagnosed with Catamenial Epilepsy. Patient was shifted to Lamotrigine but seizure exacerbations were still observed, prompting referral to the Reproductive Medicine service for adjunctive hormonal therapy. Depot medroxyprogesterone acetate was added to the antiepileptic drug which provided seizure control. Adjunctive hormonal therapy proved to be helpful in the management of intractable seizures in this patient.The report aims to give a better understanding of the neuroactive properties of estrogen and progesterone and its role in the development of Catamenial Epilepsy. Gender-related and psychosocial issues in the treatment of Epilepsy in the child-bearing years up to the menopause are also discussed.

A case report on catamenial epilepsy / Philippine Journal of Obstetrics and Gynecology

A case of a 17-year-old nulligravid with onset of seizure episodes since menarcheis reported. She was diagnosed with Seizure Disorder treated with Phenobarbital and was seizure free for 2 years. Two years prior to consult, seizure recurrences were noted to coincide with menstruation, hence, was diagnosed with Catamenial Epilepsy. Patient was shifted to Lamotrigine but seizure exacerbations were still observed, prompting referral to the Reproductive Medicine service for adjunctive hormonal therapy. Depot medroxyprogesterone acetate was added to the antiepileptic drug which provided seizure control. Adjunctive hormonal therapy proved to be helpful in the management of intractable seizures in this patient. The report aims to give a better understanding of the neuroactive properties of estrogen and progesterone and its role in the development of Catamenial Epilepsy. Gender-related and psychosocial issues in the treatment of Epilepsy in the child-bearing years up to the menopause are also discussed.

Efficacy of treatments with toltrazuril 7. 5% and lasalocid sodium in sheep naturally infected with Eimeria spp / Eficácia de tratamentos com toltrazuril 7, 5% e lasalocida sódica em ovinos naturalmente infectados com Eimeria spp

Abstract The objective of this study was to evaluate the efficacy of an experimental formulation of toltrazuril 7.5% + Trimix™ on a naturally acquired infection of Eimeria spp. in suckling lambs kept on pasture and, in another trial, evaluate the comparative efficacy between lasalocid and toltrazuril 7.5% + Trimix™ in newly weaned sheep under feedlot conditions that had been naturally infected with Eimeria spp. In the first experiment, 30 suckling lambs were divided into two groups: A - treated with toltrazuril 7.5% + Trimix™ and B- control. In experiment 2, 30 weaned sheep were divided into three groups: I - treated with toltrazuril 7.5% + Trimix™, II - treated with lasalocid and III - control. Treatment group A showed an efficacy of 90, 99.4 and 87.3% on days 5, 10 and 20, respectively. Treatment group I had an efficacy of 98.2, 92.6 and 94.5%, while group II had an efficacy of 72.7, 81.6 and 95.9% on days 7, 21 and 42, respectively. Eight Eimeria species were identified; E. ovinoidalis was the most common. Treatment with the toltrazuril 7.5% +Trimix ™ formulation was effective against Eimeria spp. in suckling lambs in field conditions and lambs weaned in under feedlot conditions.

Resumo O objetivo deste estudo foi avaliar a eficácia de uma formulação experimental de toltrazuril 7,5% + Trimix™ em cordeiros mantidos em pastagem com infecção naturalmente adquirida por Eimeria spp. e, em outro teste, a eficácia comparativa entre lasalocida sódica e toltrazuril 7,5% + Trimix™ em ovinos recém-desmamados, naturalmente infectados com Eimeria spp. em condições de confinamento. No primeiro experimento, 30 cordeiros lactantes foram divididos em dois grupos: A - tratados com toltrazuril 7,5% + Trimix™; e B - controle. No experimento 2, 30 ovinos desmamados foram divididos em três grupos: I - tratados com toltrazuril 7,5% + Trimix™; II - tratados com lasalocida sódica; e III - controle. O grupo A (tratado) obteve uma eficácia de 90, 99,4 e 87,3% nos dias 5, 10 e 20, respectivamente. O grupo I teve eficácia de 98,2, 92,6 e 94,5%, enquanto o grupo II teve uma eficácia de 72,7, 81,6 e 95.9% nos dias 7, 21 e 42, respectivamente. Foram identificadas oito espécies de Eimeria sendo E. ovinoidalis a mais comum. O tratamento com a formulação de toltrazuril 7,5% + Trimix™ foi eficaz contra Eimeria spp. em cordeiros em lactação em condições de campo e em ovinos desmamados em confinamento.

Lamotrigine monotherapy in children with epilepsy: a systematic review / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and safety of lamotrigine monotherapy in children with epilepsy via a systematic review.</p><p><b>METHODS</b>PubMed, Cochrane, CNKI, VIP, CBM, Wanfang Data were searched for randomized controlled trials (RCTs) of lamotrigine monotherapy in children with epilepsy. Literature screening, data extraction, and quality assessment were performed according to the method recommended by Cochrane Collaboration. RevMan 5.2 software was used to conduct the Meta analysis.</p><p><b>RESULTS</b>A total of 9 RCTs involving 1 016 participants were included. Lamotrigine yielded a significantly lower complete control rate of seizure than ethosuximide, but the complete control rate of seizure showed no significant differences between lamotrigine and carbamazepine/sodium valproate. Patients treated with lamotrigine had a significantly lower incidence rate of adverse events than those treated with carbamazepine, but the incidence rate of adverse events showed no significant differences between patients treated with lamotrigine and sodium valproate/carbamazepine. The drop-out rate showed no significant differences between the three treatment groups.</p><p><b>CONCLUSIONS</b>Lamotrigine is an ideal alternative drug for children who do not respond to traditional antiepileptic medication or experience significant adverse reactions; however, more high-quality RCTs with a large sample size and a long follow-up time are needed to confirm these conclusions.</p>

HLA Allele Frequencies in 5802 Koreans: Varied Allele Types Associated with SJS/TEN According to Culprit Drugs

PURPOSE: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are very serious forms of drug-induced cutaneous adverse reaction. SJS/TEN induced by certain drug is well known to be associated with some human leukocyte antigen (HLA) gene type. We aimed to explore HLA allele frequencies and their association with SJS/TEN according to culprit drugs in Korea. MATERIALS AND METHODS: We enrolled 5802 subjects who had results of HLA typing test from August 2005 to July 2014. Total 28 SJS/TEN patients were categorized based on culprit drugs (allopurinol, lamotrigine, carbamazepine) and identified the presence of HLA-B*58:01, HLA-B*44:03, HLA-B*15:02, and HLA-A*31:01. RESULTS: HLA-A*24:02 (20.5%), HLA-B*44:03 (10.0%), and HLA-Cw*01:02 (17.1%) were the most frequent type in HLA-A, -B, and -C genes, respectively. Allele frequencies of HLA-B*58:01, HLA-B*44:03, HLA-A*31:01, and HLA-B*15:02 were 7.0%, 10.0%, 5.0%, and 0.3%, respectively. In 958 allopurinol users, 9 subjects (0.9%) were diagnosed with SJS/TEN. Among them, 8 subjects possessed HLA-B*58:01 allele. SJS/TEN induced by allopurinol was more frequently developed in subjects with HLA-B*58:01 than in subjects without it [odds ratio: 57.4; confidence interval (CI) 7.12-463.50; p<0.001]. Allopurinol treatment, based on screening by HLA-B*58:01 genotyping, could be more cost-effective than that not based on screening. HLA-B*44:03 may be associated with lamotrigine-induced SJS/TEN (odds ratio: 12.75; CI 1.03-157.14; p=0.053). Among carbamazepine users, only two patients experienced SJS/TEN and possessed neither HLA-B*15:02 nor HLA-A*31:03. CONCLUSION: HLA gene frequencies varied in Korea. Screening of HLA-B*58:01 before the use of allopurinol might be needed to anticipate probability of SJS/TEN.

Effects of vardenafil on the kidney of Wistar rats submitted to acute ischemia and reperfusion

PURPOSE: To investigate the effect of vardenafil in kidney of rats submitted to acute ischemia and reperfusion. METHODS: Twenty-eight rats were randomly distributed into two groups. Right nephrectomy was performed and the vardenafil group received vardenafil solution (at a concentration of 1 mg/ml in 10 mg/kg) while the control group received 0.9% saline solution (SS) one hour prior to the ligature of the left renal pedicle. After one hour of ischemia, animals were submitted to twenty-four hours of reperfusion, followed by left nephrectomy. The kidney's histological parameters evaluated on the study included vacuolar degeneration and tubular necrosis. Apoptosis was assessed by immunohistochemistry for cleaved caspase-3 using the point-counting and digital methods (Cytophotometry). Also, a biochemical analysis for creatinine was conducted. RESULTS: There were statistically significant differences between groups only with regards to the vacuolar degeneration parameter and to the cleaved caspase-3 digital method. CONCLUSION: Vardenafil showed a protective effect on the kidney of rats subjected to acute ischemia and reperfusion in this model .

Liver dysfunction induced by systemic hypersensitivity reaction to lamotrigine: case report

Lamotrigine is an anticonvulsant drug used to treat partial and generalized seizure disorders. Hypersensitivity to lamotrigine usually causes mild symptoms such as fever, rash, and slight invasion of internal organs. However, a 33-year-old male patient who was admitted with Stevens-Johnson syndrome after taking lamotrigine for 15 days experienced hepatic failure and died 5 days after admission. This case demonstrates the importance of realizing that lamotrigine can lead to fatal hepatic failure, and that tests for the normal liver function should be performed when administering lamotrigine.

Effect of Diclazuril on the Bursa of Fabricius Morphology and SIgA Expression in Chickens Infected with Eimeria tenella

The effects of diclazuril on the bursa of Fabricius (BF) structure and secretory IgA (SIgA) expression in chickens infected with Eimeria tenella were examined. The morphology of the BF was observed by hematoxylin and eosin staining, while ultrastructural changes were monitored by transmission electron microscopy. E. tenella infection caused the BF cell volumes to decrease, irregularly arranged, as well as, enlargement of the intercellular space. Diclazuril treatment alleviated the physical signs of damages associated with E. tenella infection. The SIgA expression in BF was analyzed by immunohistochemistry technique. The SIgA expression increased significantly by 350.4% (P<0.01) after E. tenella infection compared to the normal control group. With the treatment of diclazuril, the SIgA was relatively fewer in the cortex, and the expression level was significantly decreased by 46.7% (P<0.01) compared with the infected and untreated group. In conclusion, E. tenella infection in chickens induced obvious harmful changes in BF morphological structure and stimulated the expression of SIgA in the BF. Diclazuril treatment effectively alleviated the morphological changes. This result demonstrates a method to develop an immunological strategy in coccidiosis control.

Long-term Effectiveness of Antiepileptic Drug Monotherapy in Partial Epileptic Patients: A 7-year Study in an Epilepsy Center in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It is important to choose an appropriate antiepileptic drug (AED) to manage partial epilepsy. Traditional AEDs, such as carbamazepine (CBZ) and valproate (VPA), have been proven to have good therapeutic effects. However, in recent years, a variety of new AEDs have increasingly been used as first-line treatments for partial epilepsy. As the studies regarding the effectiveness of new drugs and comparisons between new AEDs and traditional AEDs are few, it is determined that these are areas in need of further research. Accordingly, this study investigated the long-term effectiveness of six AEDs used as monotherapy in patients with partial epilepsy.</p><p><b>METHODS</b>This is a retrospective, long-term observational study. Patients with partial epilepsy who received monotherapy with one of six AEDs, namely, CBZ, VPA, topiramate (TPM), oxcarbazepine (OXC), lamotrigine (LTG), or levetiracetam (LEV), were identified and followed up from May 2007 to October 2014, and time to first seizure after treatment, 12-month remission rate, retention rate, reasons for treatment discontinuation, and adverse effects were evaluated.</p><p><b>RESULTS</b>A total of 789 patients were enrolled. The median time of follow-up was 56.95 months. CBZ exhibited the best time to first seizure, with a median time to first seizure of 36.06 months (95% confidential interval: 30.64-44.07). CBZ exhibited the highest 12-month remission rate (85.55%), which was significantly higher than those of TPM (69.38%, P = 0.006), LTG (70.79%, P = 0.001), LEV (72.54%, P = 0.005), and VPA (73.33%, P = 0.002). CBZ, OXC, and LEV had the best retention rate, followed by LTG, TPM, and VPA. Overall, adverse effects occurred in 45.87% of patients, and the most common adverse effects were memory problems (8.09%), rashes (7.76%), abnormal hepatic function (6.24%), and drowsiness (6.24%).</p><p><b>CONCLUSION</b>This study demonstrated that CBZ, OXC, and LEV are relatively effective in managing focal epilepsy as measured by time to first seizure, 12-month remission rate, and retention rate.</p>

Melamine Nephrotoxicity is Mediated by Hyperuricemia / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>We tested whether melamine nephrotoxicity was exacerbated by urate (a typical component of renal stones in humans) in rats with hyperuricemiainduced by the uricase inhibitor, potassium oxonate (Oxo).</p><p><b>METHODS</b>Rats were exposed to melamine or Oxo alone or combinations of melamine (200-400 mg/kg) and Oxo (200-600 mg/kg) for 3 consecutive days. Kidney injury was evaluated by renal biochemical functions, histomorphology, and lipid peroxidation. Kidney crystals were analyzed for their composition.</p><p><b>RESULTS</b>Nephrotoxicity was minimal in animals administered melamine or Oxo alone, but it was demonstrable in animals administered at least 800 mg/kg of the two compounds combined. All rats in the 400+600 (melamine+Oxo) and 400+400 mg/kg groups and 4 out of 6 in the 200+600 mg/kg group died within 3 days; no rat died in the 200+400 or 200+200 mg/kg group. Dose-dependent renal damage resembling clinical findings in affected patients was observed in rats administered the two compounds. Crystal composition determination revealed the existence of melamine and uric acid in the affected kidneys, resembling human stones.</p><p><b>CONCLUSION</b>Our findings suggest that uric acid plays a key role in melamine-related kidney injury in humans. Future studies should consider uric acid together with melamine when examining adverse effects in humans.</p>