Regulative effect of Taohong Siwu decoction(桃红四物汤) on extracellular matrix of endometrium in drug-induced abortion

OBJECTIVE: To explore the effects of Taohong Siwu decoction(桃红四物汤, THSWD) on the extracellular matrix of endometrium in rats following drug-induced abortion.METHODS: Thirty-six pregnant female rats were administered mifepristone and misoprostol to induce abortion, and amounts of uterine bleeding were recorded. Pathological damage and collagen accumulation were detected by hematoxylin-eosin staining and Masson’s trichrome staining in uterus, respectively. Myeloperoxidase was evaluated by immunohistochemistry.The expression levels of fibronectin, laminin, matrix metalloproteinase 9(MMP-9), and tissue inhibitor of metalloproteinase 1(TIMP-1) were quantified using western blotting.RESULTS: THSWD could promote endometrial protection in rats following drug-induced abortion.The contents of cellulose and myeloperoxidase were significantly decreased in uterine tissue of THSWD-treated groups. Moreover, THSWD significantly decreased the expression levels of fibronectin, laminin, and TIMP-1. THSWD also significantly increased MMP-9 expression and the MMP-9/TIMP-1 ratio.CONCLUSION: THSWD plays a critical role in endometrial protection by reducing extracellular matrix deposition and uterine fibrosis. These effects may have been achieved by increasing MMP-9, reducing TIMP-1, and/or altering the ratio of MMP-9/TIMP-1.

Association of Cytokines with Clinical Indicators in Patients with Drug-Induced Liver Injury

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators.Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),antiinfective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed.Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group.Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-αand IL-6 may partake the inflammatory process of DILI.

Randomized Double-Blind Controlled Clinical Study of Ciprofol and Propofol in Patients with Painless Artificial Abortion

Background and Objectives: Propofol is a commonly used intravenous anesthetic for painless artificial abortion, but the injection pain and related adverse reactions such as those related to respiration and circulation it induces have also been criticized. We aimed to conduct a comparative study on the efficacy, safety and comfort of ciprofol and propofol applied in painless artificial abortion. Materials and Methods: A total of 140 early pregnant patients undergoing painless induced abortion were selected and randomly divided into the ciprofol combined with fentanyl group (Group C) and the propofol combined with fentanyl group (Group P), with 70 cases in each group. The anesthetic effect, depth of anesthesia sedation (NI), onset time, recovery time, recovery time of orientation, retention time in the anesthesia recovery room and total amount of intravenous anesthetic drug were recorded in both groups. The respiratory rate (RR), oxygen saturation (SpO2), mean arterial pressure (MAP), and heart rate (HR) at different time points were recorded. The occurrence of perioperative adverse events, injection pain, postoperative nausea and vomiting, and dizziness were compared. The pain score at 30 minutes after operation and the satisfaction of patients and surgeons with anesthesia were evaluated. Results: The success rate of anesthesia in both groups was 100%. There were no statistically significant differences in the NI value at each time point, intraoperative body movement, recovery time, recovery time of orientation, retention time in the anesthesia recovery room, and total dosage of sedative drugs (ml) between the two groups;the onset time in Group C was longer than that in Group P, with a statistically significant difference (P Conclusion: The efficacy of ciprofol in painless induced abortion is equivalent to that of propofol, and the incidence of adverse reactions is lower than that of propofol, with higher safety and comfort.

Prevalence of Induced Abortion among Female Students in Selected Tertiary Learning Institutions in Gaborone City, Botswana

Induced abortion signifies that pregnancy has been tempered with. Abortion is the removal of an embryo or fetus weighing less than 500 grams from its mother. It can either be spontaneous (unprompted) or induced. Abortion remains one of the leading causes of maternal deaths in developing countries with induced abortion being the key cause. In 2014 from January to August, 9 abortion related deaths occurred in Botswana. There are several reasons female students in tertiary institutions resort to seeking induced abortion which include the socio-demographics like age and socio-economic factors like financial instability. Parental fears, unintended pregnancy and pressure from the partner also force females to terminate pregnancy. Induced abortion has claimed many women’s lives especially in developing countries with very restrictive abortion laws like Botswana as women do not access safe abortion care services. The study intends to establish the determinants of induced abortion among female students in selected tertiary learning institutions in Gaborone City, Botswana. It concentrated primarily on determining the prevalence of induced abortion. This was a descriptive cross-sectional study using both quantitative and qualitative data collection techniques. Systematic random sampling technique was used to come up with 278 participants. Prior to commencement of data collection, all ethical and logistical prerequisites were satisfied. Informed consent was solicited from all the study participants and the purpose of the study was fully explained. A self-administered questionnaire was used to collect data. Microsoft Excel spread sheet was used to code, clean, and enter the data, which was then exported for analysis to the statistical package for social sciences version 24. Frequency distribution tables, percentages graphs, and pie charts were used to illustrate the descriptive information. The study revealed that prevalence of induced abortion among female students in Gaborone City is 7.9%. They even suggested that induced abortion be liberalized. Age was the only socio-demographic factor associated with induced abortion with p = 0.047 using Chi Square test χ2 = 7.609, df = 3. The study findings concluded that female students resort to induced abortion as a result of pressure from both parents and male partners especially when the pregnancy is unintended. The study recommends that the abortion law in Botswana be made liberal to ease access to safe abortion care services. It also recommends that contraceptive commodities should consistently be available in public health facilities.

Spontaneous Abortions in the Second Trimester of Pregnancy: Research and Analysis of Factors Associated at Laquintinie Hospital in Douala

Introduction: Spontaneous abortion of the second trimester is an interruption of pregnancy with complete expulsion or not of the product of conception between 15 and 28 weeks of pregnancy without any maneuvers. The objective of our study was to determine the factors associated with second trimester spontaneous abortions at Laquintinie Hospital in Douala. Methodology for this purpose: We conducted a case-control study from January to May 2019 on pregnant women who may or may not have had spontaneous second trimester abortions. Results: In total we recorded 1609 pregnancies and recruited 184 patients, including 46 cases and 138 controls;which gave a frequency of spontaneous abortion in the second trimester of pregnancy of 2.85%. A correlative analysis showed that spontaneous abortions in the second trimester were associated with housewife status (OR = 2.89;CI = 1.21 - 6.79;p = 0.010), gestation > 5 (OR = 4.09;CI = 1.02 - 17.66;p = 0.040), multiparity (OR = 3.81;CI = 1.59 - 9.16;p = 0.002), history of endouterine maneuvers (OR = 5.64;CI = 2.43 - 13 .03;p = 0.000), malaria in pregnancy (OR = 3.99;CI = 1.1 - 14.76;p = 0.030), incompleteness on the second trimester ultrasound (OR = 2.37;CI = 1.18 - 4.70;p = 0.010), jolts when traveling (OR = 46.04;CI = 17.29 - 123.66;p = 0.000), long car journeys (OR = 7.05;CI = 1.99 - 27.77;p = 0.000). After logistic regression eliminating the confounding factors, only the following were associated with abortions: Multiparity (OR = 13.90;CI = 2.96 - 65.18;p = 0.000), endo uterine maneuvers (OR = 3.69;CI = 1. 01 - 13.44;p = 0.047), jolts when traveling (OR = 72.63;CI = 19.47 - 270.96;p = 0.000), long car journeys (OR = 15.41;CI = 2.7 - 85, 95;p = 0.000). Conclusion: Our study reveals that a set of factors contribute to the occurrence of spontaneous abortions in the second trimester of pregnancy in our context.

Effect of emotion management and nursing on patients with painless induced abortion after operation

BACKGROUND With an estimated 121 million abortions following unwanted pregnancies occurring worldwide each year,many countries are now committed to protecting women’s reproductive rights.AIM To analyze the impact of emotional management and care on anxiety and contraceptive knowledge mastery in painless induced abortion(IA)patients.METHODS This study was retrospective analysis of 84 patients with IA at our hospital.According to different nursing methods,the patients were divided into a control group and an observation group,with 42 cases in each group.Degree of pain,rate of postoperative uterine relaxation,surgical bleeding volume,and postoperative bleeding volume at 1 h between the two groups of patients;nursing satisfaction;and mastery of contraceptive knowledge were analyzed.RESULTS After nursing,Self-Assessment Scale,Depression Self-Assessment Scale,and Hamilton Anxiety Scale scores were 39.18±2.18,30.27±2.64,6.69±2.15,respectively,vs 45.63±2.66,38.61±2.17,13.45±2.12,respectively,with the observation group being lower than the control group(P<0.05).Comparing visual analog scales,the observation group was lower than the control group(4.55±0.22 vs 3.23±0.41;P<0.05).The relaxation rate of the cervix after nursing,surgical bleeding volume,and 1-h postoperative bleeding volumes were 25(59.5),31.72±2.23,and 22.41±1.23,respectively,vs 36(85.7),42.39±3.53,28.51±3.34,respec tively,for the observation group compared to the control group.The observation group had a better nursing situation(P<0.05),and higher nursing satisfaction and contraceptive knowledge mastery scores compared to the control group(P<0.05).CONCLUSION The application of emotional management in postoperative care of IA has an ideal effect.

Patterns of Infertility and Abortion in Saudi Arabia: A Cross-Sectional Study

Background: Infertility and abortion are significant reproductive health concerns globally, impacting individuals' well-being and healthcare systems. In Saudi Arabia, cultural, social, and religious factors influence perceptions and management of these issues, necessitating research to understand the patterns and associated factors. Study Aim: This cross-sectional study aimed to investigate the patterns of infertility and abortion among 458 women in Saudi Arabia, focusing on demographic profiles, reproductive histories, medical conditions, and lifestyle factors. Methodology: Participants were recruited from healthcare facilities, and data on age, BMI, reproductive history, medical conditions, assisted reproduction methods, and lifestyle behaviors were collected. Statistical analyses, including chi-square tests, were conducted to examine associations between variables. Results: The majority of participants were aged 30 - 39 years (47.4%), with 76.9% experiencing secondary infertility. Among those with offspring (76.9%), 31% reported using assisted reproduction methods, primarily ovarian stimulators (54.2%). Abortion history was reported by 39.5% of participants. Significant associations were found between age and infertility type (X2 = 5.8, p = 0.054), having offspring and infertility type (X2 = 458.0, p = 0.001), menstrual irregularity and infertility type (X2 = 11.4, p = 0.001), and abortion history and delayed fertility (X2 = 10.4, p = 0.001). Conclusion: Our study reveals significant associations between demographic, medical, and lifestyle factors with infertility patterns and abortion history among Saudi women. These findings emphasize the need for tailored interventions addressing medical conditions, age-related factors, and access to reproductive healthcare services.

Effects of Yigan Capsule on the expression of HMGB1,RAGE and NF-κB protein in rats with drug-induced liver injury

Objective:To study the effect of Yigan capsule on the expression of high mobility group protein B1(HMGB1),nuclear factor-B(NF-κB)and receptor for advanced glycation end products(RAGE)in anti-tuberculosis drug-induced liver injury(ATB-DILI),and to explore its protective effect and mechanism on ATB-DILI,so as to provide experimental basis for the clinical application of Yigan capsule.Methods:Twenty-four rats were divided into two groups.Except for the blank group(n=6),the other 18 rats were given isoniazid(INH)+rifampicin(RFP)(50 mg/kg.d)for 4 weeks.Then 18 rats were randomly divided into three groups(model group,low dose group of Yigan capsule and high dose group of Yigan capsule)according to 6 rats in each group.The blank group and the model group were given 0.9%sodium chloride solution by intragastric administration.The low dose group of Yigan capsule was 0.468 g/kg,and the high dose group of Yigan capsule was 1.872 g/kg[1].After 4 weeks,the pathological changes of liver were observed by HE staining.The contents of ALT,AST,ALP,γ-GT and TBIL were detected.The expression of HMGB1,NF-κBp65 and RAGE protein was detected by IHC.The expression levels of HMGB1,NF-κBp65,RAGE,TNF-αand IL-1βwere detected by WB.Result:HE staining showed that the structure of the liver in the model group was disordered,the liver cells showed swelling and fusion,the number of inflammatory cells increased and accompanied by punctate necrosis,while the above pathological changes in each treatment group of Yigan capsule were significantly improved.The contents of ALT,AST,ALP,γ-GT and TBIL in the model group were higher than those in the blank group(P<0.05).The contents of ALT,AST,ALP,γ-GT and TBIL in each treatment group were significantly lower than those in the model group(P<0.05).Compared with the blank group,the expression levels of TNF-αand IL-1βin the model group were increased(P<0.05),and the expression levels of HMGB1,NF-κBp65 and RAGE were increased(P<0.05).Compared with the model group,the expression levels of TNF-αand IL-1βin each treatment group of Yigan capsule decreased(P<0.05),and the expression of HMGB1,NF-κBp65 and RAGE decreased(P<0.05).Conclusion:Yigan capsule may inhibit the secretion of inflammatory factors through HMGB1/RAGE/NF-κBp65 signaling pathway,thus protecting ATB-DILI.

Populational change of CD4^(+)CD25^(+)Treg cells is responsible for the synergistic effect of the combination of RAMP2 with baicalin in treating recurrent spontaneous abortion mouse models

Background: The absence of a safe and effective therapy for recurrent spontaneous abortion due to a maternofetal failure in immunological tolerance remains an intractable clinical obstacle for surgeons. Recently, traditional Chinese medicine has become a feasible alternative for certain diseases, including recurrent spontaneous abortion. However, because of the complex composition of the traditional Chinese medicine formula, its action mechanism remains unclear. Methods: We selected two isolated active ingredients (RAMP and baicalin) from the traditional Chinese medicine formula and used an abortion-prone CBA/J × DBA/2 model to simulate human RSA and compared the changes in fetal resorption rate, Treg cell percentage, and relevant cytokines before and after combination therapy. In addition, The mechanisms were preliminarily discussed using in vitro differentiation models. Results: In CBA/J × DBA/2 abortion-prone mice, the combination therapy resulted in a lower embryo resorption rate compared to that obtained with individual delivery of either RAMP or baicalin, thereby playing an embryo-protective role through the increase in Treg cells for the maintenance of maternal-fetal immune tolerance. In in vitro primary cell differentiation experiments, the concentration of Treg cells significantly increased from 11% to 17.9% after the combination therapy compared to that of the single administration group. Conclusion: the synergistic effects of RAMP and baicalin were responsible for Treg differentiation. The present study provides a solid basis for improving the applicability of traditional Chinese herbs in the treatment of recurrent spontaneous abortion.

A Survey on TCM Treatment of Drug-Induced Postabortal Colporrhagia

Drug postabortal colporrhagia is one of the major problems that need to be solved in gynecoiatry. It is shown in the literature that TCM treatment of this disease has achieved quite good therapeutic effects. It is my opinion that the following works should be done for a better therapeutic effect: 1) study further the pathogeneses of the disease; 2) stipulate a unified criteria for typing, diagnosis and treatment; 3) develop specific prescriptions and new forms of preparation; and 4) further efforts should be also made on the other TCM therapies, such as acupuncture, physiotherapy, and massotherapy.

Relationship Between Litchi Embryo Abortion and Phenolic Inhibitors

Phenolic inhibitors were preliminarily isolated from the normal and abortive litchi (Litchi chinensis Sonn.) ovules with a series of solvents, and then separated and purified by thin-layer chromatography (TLC), further isolated and identified with GC-MS, and finally checked with standards. p-Hydroxybenzoic acid (p-HBA) was isolated and identified from litchi ovules in this experiment for the first time. Determination of its biological activity showed that p-HBA was a very strong growth inhibitory substance. In abortive ovules, p-HBA content and IAA oxidase activity were much higher; IAA content was much lower than those in normal ovules (P<0.01). It is suggested that p-HBA may be involved in the regulation of litchi embryo development; high content of p-HBA may accelerate IAA oxidation and affect the balance of growth promoting and inhibitory substances, causing embryo abortion.

The Relation between Anther's Nutrient Metabolism and Pollen Abortion of Male Sterile Lines in Lycium barbarum L.

[ Objective] This study deals with the relation between anther nutrient metabolism and pollen abortion of male sterile lines in Lycium barbarum L., and provides some theoretical references for the pollen abortion mechanism of male sterile lines in Lyciurn barbarurn L.. [Method] By using semi-thin section and cytochemistry technology, the accumulation and distribution of anther nutrient of male sterile and fertile lines in Lycium barbarum L. were observed and compared. [ Result] The result showed that after meiosis, starch grains in the connective parenchyma of anther decreased sharply, and starch grains in epidermis and endothecium were also greatly decreased, while nearly no lipid accumulated in tapetal cells in male sterile lines compared with the fertile lines. The tapetal cells and tetraspore had vacuoles appear successively, and then entered the degenerate process. During the degeneration stage of tapetal cells and tetraspore, starch grains in epidermis and endothecium were still in a smell number and in the connective parenchyme as well. [ Conclusion] The decrease of polysaccharide supplying in anther vascular leads to the disorder of mechanism of glycelipid transforming in tapetal ceils, which triggers the tapetal cells degenerating ahead of time, and the latter gives rise to callus wall failing to degenerate in time. Therefore, the tetrads disintegrate and disappear ultimately due to lack of nutrition.

Study on Relation between Endogenous Phytohormones and Ovule Abortion in Tetraploid Robinia pseudoacacia

This study was conducted to investigate ovule abortion of tetraploid Robinia pseudoacacia and its reasons. It was found that in the ovule development period of tetraploid R. pseudoacacia from 15 d after coronal opening, the levels of growth-promoting endogenous hormones in abortive ovules were lower than those in normal ovules, and the level of a growth-inhibiting hormone was always higher than those in normal ovules, indicating that ovule abortion of tetraploid R. pseudoacacia might be related to abnormal endogenous phytohormones in ovules. This study laid a foundation for further study on highly sterile phenomenon of tetraploid R. pseudoacacia seeds.

Study on prevention effect of Zishen Yutai pill combined with progesterone for threatened abortion in rats

Objective:To observe preventive and therapeutic effects and the mechanism of actions on Zishen Yutai pill combined with progesterone on threatened abortion in rats.Methods:After pregnancy,50 SPF female SD rats were selected and divided into control group,model group,progesterone group,Zishen Yutai pill group,and progesterone plus Zishen Yutai pill group(combination group),with 10 rats in each group.The rats of control group and abortion model group were lavaged with 2 mL/kg normal saline on pregnancy day 1 for continuous 10 days.Rats in Zishen Yutai pill group were given 1.575 g/kg/d of Zishen Yutai pill for intragastric administration for continuous 10 days.Rats in progesterone group were given intramuscular injection treatment of 0.1 mL/d progestin,continuous for 10 days.Rats in combination group were given injection therapy of aqueous solution of Zishen Yutai pill for continuous 10 days,and other treatments were the same as previous two groups.Abortion model were established then and live births,numbers of abortion and average rate of abortion were compared between the five groups.Peripheral blood was collected to detect the estradiol(E2) and progestational hormone(P),and obtain ratio of Th1/Th2 cytokines(IL-2,INF-γ,IL-4,IL-10).Results:Significant more live births of rats were found in the control group compared with other four groups(P<0.05).The numbers of live births of the rats in abortion model group were significantly less than that of progesterone group,Zishen Yutai pill group and joint group(P<0.05).The numbers of live births of rats in joint group were significant more than that of progesterone group and Zishen Yutai pill group.The serum E2 level of P of rats in the control group,progesterone group,Zishen Yutai pill group and joint group were significant higher than that of abortion model group(P<0.05).Serum levels of E2 and P of rats in the control group,progesterone group,Zishen Yutai pill group and joint group were not significant different(P>0.05) but these levels in the control group and Zishen Yutai pill group were significant lower than that of progesterone group and joint group(P<0.05).The maternal-fetal interface IL-4/IL-2,IL-10 / IL-2 of model group were balanced deviating to Th1,while the IL-4/IL-2,IL-10/IL-2 of progesterone group,Zishen Yutai pill group and joint group were balanced deviating to Th2,and joint group' deviation was better than progesterone group and Zishen Yutai pill group(P<0.05).Conclusions:Zishen Yutai pill combined with progesterone has a significant control effect for threatened abortion,which can obviously increase contents of maternal serums E2 and P,and regulate the Thl/Th2 balance with a remarkable effect.

drug-induced autoimmune liver disease:a diagnostic dilemma of an increasingly reported disease

The aetiology of autoimmune hepatitis(AIH) is uncer-tain but the disease can be triggered in susceptible patients by external factors such as viruses or drugs.AIH usually develops in individuals with a genetic back-ground mainly consisting of some risk alleles of the major histocompatibility complex(HLA).Many drugs have been linked to AIH phenotypes,which sometimes persist after drug discontinuation,suggesting that they awaken latent autoimmunity.At least three clini-cal scenarios have been proposed that refers to drug- induced autoimmune liver disease(DIAILD):AIH with drug-induced liver injury(DILI); drug induced-AIH(DI-AIH); and immune mediated DILI(IM-DILI).In addi-tion,there are instances showing mixed features of DI-AIH and IM-DILI,as well as DILI cases with positive autoantibodies.Histologically distinguishing DILI from AIH remains a challenge.Even more challenging is the differentiation of AIH from DI-AIH mainly relying in histological features; however,a detailed standard-ised histologic evaluation of large cohorts of AIH and DI-AIH patients would probably render more subtle features that could be of help in the differential diag-nosis between both entities.Growing information on the relationship of drugs and AIH is being available,being drugs like statins and biologic agents more fre-quently involved in cases of DIAILD.In addition,there is some evidence on the fact that patients diagnosed with DIAILD may have had a previous episode of hepa-totoxicity.Further collaborative studies in DIAILD will strengthen the knowledge and understanding of this intriguing and complex disorder which might represent different phenotypes across the spectrum of

Practical guidelines for diagnosis and early management of drug-induced liver injury

The spectrum of drug-induced liver injury （DILI） is both diverse and complex. The first step in diagnosis is a suspicion of DILl based on careful consideration of recent comprehensive reports on the disease. There are some situations in which the suspicion of DILI is particularly strong. Exclusion of other possible etiologies according to the pattern of liver injury is essential for the diagnosis. In patients with suspected DILl, diagnostic scales, such as the Councils for International Organizations of Medical Sciences/ Roussel Uclaf Causality Assessment Method （CIOMS/RUCAM） scale, may be helpful for the final diagnosis. Early management of DILl involves prompt withdrawal of the drug suspected of being responsible, according to serum levels of alanine aminotransferase （ALT）, alkaline phosphatase （ALP）, and total bilirubin （T-Bil）. However, as DILI patients may show resolution of liver injury without discontinuation of the drug, it should be carefully evaluated whether the suspected drug should be discontinued immediately with adequate consideration of the importance of the medication.

Changes of Oxidative Stress and Soluble Sugar in Anthers Involve in Rice Pollen Abortion Under Drought Stress

Two rice maintaining lines with different drought tolerances, viz., Jin 23B （tolerant） and Zhenshan 97B （sensitive）, were used to study the oxidative stress and soluble sugar in rice anthers and pollen viability under drought stress during flowering stage. Higher antioxidant enzyme activities and lower malonaldehyde （MDA） content in rice anthers were observed in Jin 23B than in Zhenshan 97B under drought stress. Further, a great increase in the content of soluble sugar in rice anthers of Jin 23B was observed across the whole drought exposure, while Zhenshan 97B showed significant decrease in soluble sugar during 9-12 d after drought stress （DADS）. Accordingly, a marked decline of pollen fertility and activity, pollen numbers in an anther and pollen numbers on a stigma was observed in Zhenshan 97B, whereas little difference was found in Jin 23B. Thus, we suggest that pollen abortion caused by drought stress may be related with the reciprocity between oxidative stress and soluble sugar content in rice anthers.

Drug-induced liver injury:Is it somehow foreseeable?

The classic view on the pathogenesis of drug-induced liver injury is that the so-called parent compounds are made hepatotoxic by metabolism (formation of neosubstances that react abnormally), mainly by cytochromes P-450 (CYP), with further pathways, such as mitochondrial dysfunction and apoptosis, also playing a role. Risk factors for drug-induced liver injury include concomitant hepatic diseases, age and genetic polymorphisms of CYP. However, some susceptibility can today be predicted before drug administration, working on the common substrate, by phenotyping and genotyping studies and by taking in consideration patients' health status. Physicians should always think of this adverse effect in the absence of other clear hepatic disease. Ethical and legal problems towards operators in the health care system are always matters to consider.

NAT2＊6A, a haplotype of the N-acetyltransferase 2 gene, is an important biomarker for risk of anti-tuberculosis drug-induced hepatotoxicity in Japanese patients with tuberculosis

AIM: To investigate an association between N -acetyltransferase 2 (NAT2 )-haplotypes/diplotypes and adverse effects in Japanese pulmonary tuberculosis patients. METHODS: We studied 100 patients with pulmonary TB treated with anti-TB drugs including INH. The frequencies and distributions of single nucleotide polymorphisms, haplotypes, and diplotypes of NAT2 were determined by the PCR-restriction fragment length polymorphism method, and the results were compared between TB patients with and without adverse effect, using multivariate logistic regression analysis.RESULTS: Statistical analysis revealed that the frequency of a variant haplotype, NAT2*6A , was signifi cantly increased in TB patients with hepatotoxicity, compared with those without hepatotoxicity [P = 0.001, odds ratio (OR) = 3.535]. By contrast, the frequency of a wild-type (major) haplotype, "NAT2*4", was signif icantly lower in TB patients with hepatotoxicity than those without hepatotoxicity (P < 0.001, OR = 0.265). There was no association between NAT2-haplotypes and skin rash or eosinophilia. CONCLUSION: The present study shows that NAT2 is one of the determinants of anti-TB drug-induced hepatotoxicity. Moreover, the haplotypes, NAT2*4 and NAT2*6A, are useful new biomarkers for predicting anti- TB drug-induced hepatotoxicity.

Assessment of drug-induced hepatotoxicity in clinical practice: A challenge for gastroenterologists

Currently, pharmaceutical preparations are serious contributors to liver disease; hepatotoxicity ranking as the most frequent cause for acute liver failure and post-commercialization regulatory decisions. The diagnosis of hepatotoxicity remains a difficult task because of the lack of reliable markers for use in general clinical practice. To incriminate any given drug in an episode of liver dysfunction is a step-by-step process that requires a high degree of suspicion, compatible chronology, awareness of the drug’s hepatotoxic potential, the exclusion of alternative causes of liver damage and the ability to detect the presence of subtle data that favors a toxic etiology. This process is time-consuming and the final result is frequently inaccurate. Diagnostic algorithms may add consistency to the diagnostic process by translating the suspicion into a quantitative score. Such scales are useful since they provide a framework that emphasizes the features that merit attention in cases of suspected hepatic adverse reaction as well. Current efforts in collecting bona fide cases of drug-induced hepatotoxicity will make refinements of existing scales feasible. It is now relatively easy to accommodate relevant data within the scoring system and to delete low-impact items. Efforts should also be directed toward the development of an abridged instrument for use in evaluating suspected drug-induced hepatotoxicity at the very beginning of the diagnosis and treatment process when clinical decisions need to be made. The instrument chosen would enable a confident diagnosis to be made on admission of the patient and treatment to be fine-tuned as further information is collected.