土家族治毒药的配伍使用规律研究

基于土家治毒药理论,分析土家治毒药的组方用药规律,为进一步挖掘土家医药方剂用药规律提供参考。通过对药物名称标准化后,建立土家医方剂和治毒药数据库,对治毒药性-味关系、土家医方剂中治毒药使用频次、常用治毒药与非治毒药组合等进行统计分析,得到20个出现频次最高的药物组合。研究表明,土家治毒药药性多属寒、凉,药味以苦、甘、辛居多;治毒药在土家医方剂中的使用频次较低;治毒药在方剂中多作为主药、帮药使用,其在土家医用药体系中发挥着重要作用;相对使用频次高的治毒药物有大血藤、血当归、土茯苓、五爪龙、水菖蒲和蛇莓等,与之相配的药物有小血藤、三百棒、月季花、甘草和车前草等。本研究旨在探索治毒药在复方中的使用规律,验证了治毒药在土家方剂中的重要地位,为完善土家方剂挖掘整理、组方配伍规律分析奠定了基础。

Study on the Effective Prevention and Control of Maize Rough Dwarf Disease in Different Areas with Varying Epidemic Intensity in Shandong Province

[ Objective] This study aimed to investigate the effective prevention and control of maize rough dwarf disease in different areas with varying epidemic inten-sity in Shandong Province. [Method] Control effects of single application of virus in-hibitors and composite application of virus inhibitors with seed dressing agents and pesticides on maize rough dwarf disease in different areas with varying epidemic intensity were investigated. [Result] The same treatment possessed entirely different effects in severely affected areas and slightly affected areas. To be specific, single application of virus inhibitors in slightly affected areas exhibited good control effects, with a control efficiency of 76.59% and yield increment rate of 158.21%; in severely affected areas, single application of virus inhibitors led to low control efficiency and yield increment rate. The highest control efficiency of composite application of virus inhibitors with seed dressing agents and pesticides in severely affected areas was 71.38%, and experimental plots changed from total crop failure to have certain eco-nomic output. [Conclusion] ln different areas with varying epidemic intensity of maize rough dwarf disease, different application modes should be adopted according to lo-cal conditions, thereby saving cost and improving control efficiency.

Peginterferon and ribavirin treatment for hepatitis C virus infection

Pegylated interferon α (IFNα) in combination with ribavirin is currently recommended as a standard-of-care treatment for chronic hepatitis C virus (HCV) infection. This combination therapy has drastically improved the rate of sustained virological response, specifically in difficult-to-treat patients. Recently, individualized treatment, such as response-guided therapy, is being developed based on host-, HCV- and treatment-related factors. Furthermore, modified regimens with currently available medications, novel modified IFNα and ribavirin or combinations with specifically targeted antiviral therapy for HCV agents, are currently being investigated. The purpose of this review is to address some issues and epoch-making topics in the treatment of chronic HCV infection, and to discuss more optimal and highly individualized therapeutic strategies for HCV-infected patients.

A General Introduction of HIV/AIDS Treatment with Traditional Chinese Medicine in China

This paper gives a general introduction of HIV/AIDS treatment with Traditional Chinese Medicine (TCM) in China during the past 20 years. Although the role of TCM in treatment of HIV/AIDS is promising,there is still a long way to go.

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.

Effects of a 24-week course of interferon-αtherapy after curative treatment of hepatitis C virus-associated hepatocellular carcinoma

AIM： To assess whether a 24-wk course of interferon （IFN） could prevent hepatocellular carcinoma （HCC） recurrence and worsening of liver function in patients with hepatitis C virus （HCV）-infected patients after receiving curative treatment for primary HCC.METHODS： Outcomes in 42 patients with HCV infection treated with IFN-α, after curative treatment for primary HCC （IFN group）, were compared with 42 matched curatively treated historical controls not given IFN （non- IFN group）.RESULTS： Although the rate of initial recurrence did not differ significantly between ]FN group and non-IFN group （0%, 44%, 61~, and 67% ys 4.8%, 53~, 81%, and 87% at 1, 3, 5, and 7 years, P = 0.153, respectively）, ]FN group showed a lower rate than the non-IFN group for second recurrence （0%, 10.4%, 28%, and 350/0 ys 0%, 30~ , 59%, and 66% at 1, 3, 5 and 7 years, P = 0.022, respectively）. Among the ]FN group, patients with sustained virologic response （SVR） were less likely to have a second HCC recurrence than ]FN patients without an SVR, or non-IFN patients. Multivariate analysis identified the lack of SVR as the only independent risk factor for a second recurrence, while SVR and Child-Pugh class A independently favored overall survival.CONCLUSION： Most intrahepatic recurrences of HCV-related HCC occurred during persistent viral infection. Eradication of HCV is essential for the prevention of HCC recurrence and improvement of survival.

Triple antiviral therapy in HCV positive patients who failed prior combination therapy

AIM： To assess the efficacy of triple therapy （peginterferon or high dose standard interferon, plus ribavirin and amantadine） in nonresponders to prior combination therapy. METHODS： A total of 196 patients were enrolled in a multicenter, open, randomized study. Patients were given 180 μg/wk of peginterferon-alpha-2a （40 kD） plus ribavirin （800-1000 rag/d） and amantadine （200 rag/d） for 48 wk （group A） or interferon-alpha-2a （6 MU/d for 4 wk, 3 MU/d for 20 wk, and 3 MU tiw for 24 wk） plus ribavirin （800-1000 rag/d） and amantadine （200 rag/d） for 48 wk （group B）. RESULTS： Overall sustained virologic response （SVR） was 26.6% （32.1% and 19.5% in group A and B, P = 0.057）. Baseline ALT 〉120 UI/L （OR 2.4; 95% CI：1.11 to 5.20; P = 0.026） and HCV RNA negativity after 12 wk （OR 8.7; 95% CI： 3.87 to 19.74; P 〈 0.0001） were independently associated with SVR. Therapy discontinuation occurred less frequently in patients treated with peginterferon than standard interferon （P = 0.036）. CONCLUSION： More than 25% of nonresponders to combination therapy can eradicate HCV infection when retreated with triple therapy, especially if they have a high baseline ALT and are treated with pegylated interferon.

Prevention and Treatment of KSHV-associated Diseases with Antiviral Drugs

Kaposi’s sarcoma-associated herpesvirus (KSHV) was first identified as the etiologic agent of Kaposi’s sarcoma (KS) in 1994. KSHV infection is necessary,but not sufficient for the development of Kaposi sarcoma (KS),primary effusion lymphoma (PEL),and multicentric Castleman disease (MCD). Advances in the prevention and treatment of KSHV-associated Diseases have been achieved,even though current treatment options are ineffective,or toxic to many affected persons. The identification of new targets for potential future therapies and the randomized trial to evaluate the efficacy of new antivirals are required.

In vitro screening of traditionally used medicinal plants in China against Enteroviruses

AIM： To search for new antiviral agents from traditional Chinese medicine, specifically anti-enterovirosuses agents. METHODS： The aqueous extracts （AE） of more than 100 traditionally used medicinal plants in China were evaluated for their in vitro anti-Coxsackie virus B3 activities with a MTT-based colorimetric assay. RESULTS： The test for AE of 16 plants exhibited anti- Coxsackie virus B3 activities at different magnitudes of potency. They can inhibit three steps （inactivation, adsorption and replication） during the infection. Among the 16 plants, Sargentodoxa cuneata （Oliv.） Rehd. et Wils., Sophora tonkinensis Gapnep., Paeonia veitchii Lynch, Spatholobus suberectus Dunn. and Cyrtorniurn fortunei J, sm. also have activity against other enterovirus, including Coxsackie virus 135, Polio virus I, Echo virus 9 and Echo virus 29. Cell cytotoxic assay demonstrated that all tested AE had CC50 values higher than their EC50 values. CONCLUSION： The sixteen traditionally used medicinal plants in China possessed antMral activity, and some of them merit further investigations.

Development of Novel Antiviral Therapies for Hepatitis C Virus

Over 170 million people worldwide are infected with hepatitis C virus (HCV), a major cause of liver diseases. Current interferon-based therapy is of limited efficacy and has significant side effects and more effective and better tolerated therapies are urgently needed. HCV is a positive, single-stranded RNA virus with a 9.6 kb genome that encodes ten viral proteins. Among them, the NS3 protease and the NS5B polymerase are essential for viral replication and have been the main focus of drug discovery efforts. Aided by structure-based drug design, potent and specific inhibitors of NS3 and NS5B have been identified, some of which are in late stage clinical trials and may significantly improve current HCV treatment. Inhibitors of other viral targets such as NS5A are also being pursued. However, HCV is an RNA virus characterized by high replication and mutation rates and consequently, resistance emerges quickly in patients treated with specific antivirals as monotherapy. A complementary approach is to target host factors such as cyclophilins that are also essential for viral replication and may present a higher genetic barrier to resistance. Combinations of these inhibitors of different mechanism are likely to become the essential components of future HCV therapies in order to maximize antiviral efficacy and prevent the emergence of resistance.

Current progress in the treatment of chronic hepatitis C

Over the last decade, the standard of care for the treat- ment of chronic hepatitis C has been the combination of pegylated-interferon-alfa （PEG-IFN） and ribavirin （RBV） which results in sustained virological response （SVR） rates of 75%-85% in patients with genotypes 2 or 3 but only of 40%-50% in patients with genotype 1. Cur- rently, there are rapid and continuous developments of numerous new agents against hepatitis C virus （HCV）, which are the focus of this review. Boceprevir and tela- previr, two first-generation NS3/4A HCV protease inhibi- tors, have been recently licensed in several countries around the world to be used in combination with PEG- IFN and RBV for the treatment of genotype 1 patients. Boceprevir or telaprevir based triple regimens, com- pared with the PEG-IFN/RBV combination, improve the SVR rates by 25%-31% in treatment-naTve genotype 1 patients, by 40%-64% in prior relapsers, by 33%-45% in prior partial responders and by 24%-28% in prior null responders. At the same time, the application of response-guided treatment algorithms according to the on-treatment virological response results in shortening of the total therapy duration to only 24 wk in 45%-55% of treatment-na＇ive patients. There are, however, several challenges with the use of the new triple combinations in genotype 1 patients, such as the need for immediate results of HCV RNA testing using sensitive quantitative assays, new and more frequent adverse events （anemia and dysgeusia for boceprevir; pruritus, rash and anemia for telaprevir）, new drug interactions and increasing dif- ficulties in compliance. Moreover, the SVR rates are still poor in very difficult to treat subgroups of genotype 1 patients, such as null responders with cirrhosis, while there is no benefit for patients who cannot tolerate PEG- IFN/RBV or who are infected with non-1 HCV genotype. Many newer anti-HCV agents of different classes and numerous combinations are currently under evaluation with encouraging results. Preliminary data suggest that the treatment of chronic HCV patients with well toler- ated combinations of oral agents without PEG-IFN is feasible and may lead to a universal HCV cure over the next 5-10 years.

Effect of sustained virological response on long-term clinical outcome in 113 patients with compensated hepatitis C-related cirrhosis treated by interferon alpha and ribavirin

AIM： To assess the long-term clinical benefit of sustained virological response （SVR） in patients with hepatitis C virus （HCV） cirrhosis treated by antiviral therapy using mostly ribavirin plus interferon either standard or pegylated.METHODS： One hundred and thirteen patients with uncomplicated HCV biopsy-proven cirrhosis, treated by at least one course of antiviral treatment ≥ 3 mo and followed ≥ 30 mo were included. The occurrence of clinical events [hepatocellular carcinoma （HCC）, decompensation and death] was compared in SVR and non SVR patients.RESULTS： Seventy eight patients received bitherapy and 63 had repeat treatments. SVR was achieved in 37 patients （33%）. During a mean follow-up of 7.7 years, clinical events occurred more frequently in non SVR than in SVR patients, with a significant difference for HCC （24/76 vs 1/37, P = 0.01）. No SVR patient died while 20/76 non-SVR did （P = 0.002）, mainly in relation to HCC （45%）.CONCLUSION： In patients with HCV-related cirrhosis, $VR is associated with a significant decrease in the incidence of HCC and mortality during a follow-up period of 7.7 years. This result is a strong argument to perform and repeat antiviral treatments in patients with compensated cirrhosis.

Defensive nature of Sargassum polycystum (Brown alga) against acetaminophen-induced toxic hepatitis in rats: Role of drug metabolizing microsomal enzyme system, tumor necrosis factor-a and fate of liver cell structural integrity

AIM： To assess the defensive nature of Sargassum polycystum （S. polycystum） （Brown alga） against acetaminophen （AAP）-induced changes in drug metabolizing microsomal enzyme system, tumor necrosis factor （TNF-α） and fine structural features of the liver during toxic hepatitis in rats. METHODS： Male albino Wistar strain rats used for the study were randomly categorized into 4 groups. Group Ⅰ consisted of normal control rats fed with standard diet. Group II rats were administered with acetaminophen （800 mg/kg body weight, intraperitoneally）. Group Ⅲ rats were pre-treated with S. polycystum extract alone. Group IV rats were orally pre-treated with S. polycystum extract （200 mg/kg body weight for 21 d） prior to acetaminophen induction （800 mg/kg body weight, intraperitoneally）. Serum separated and liver was excised and microsomal fraction was isolated for assaying cytochrome P450, NADPH Cyt P450 reductase and bs. Serum TNF-α was detected using ELISA. Fine structural features of liver were examined by transmission electron microscopy. RESULTS： Rats intoxicated with acetaminophen showed considerable impairment in the activities of drug metabolizing microsomal enzymes, such as cytochrome P450, NADPH Cyt P450 reductase and bs when compared with the control rats. The rats intoxicated with acetaminophen also significantly triggered serum TNF-a when compared with the control rats. These severe alterations in the drug metabolizing enzymes were appreciably pretreated with S. polycystum. prevented in the rats The rats pretreated withS. polycystum showed considerable inhibition in the elevation of TNF-α compared to the rats intoxicated with acetaminophen. The electron microscopic observation showed considerable loss of structural integrity of the endoplasmic reticulum, lipid infiltration and ballooning of mitochondria in the acetaminophen-intoxicated rats, whereas the rats treated with S. polycystum showed considerable protection against acetaminophen-induced alterations in structural integrity. CONCLUSION： These observations suggest that the animals treated with S. polycystum extract may have the ability to protect the drug metabolizing enzyme system and mitochondrial functional status from free radical attack, thereby showing its defense mechanism in protecting hepatic cells from acetaminophen toxic metabolite N-acetyl-para-benzoquinone-imine （NAPQI）.

Current prophylactic strategies against hepatitis B virus recurrence after liver transplantation

Prophylactic strategies against hepatitis B virus(HBV) recurrence after liver transplantation(LT) are essential for patients with HBV-related disease.Before LT, lamivudine(LAM) was proposed to be down-graded from first-to second-line therapy.In contrast, adefovir dipivoxil(ADV) has been approved not only as first-line therapy but also as rescue therapy for patients with LAM resistance.Furthermore, combination of ADV and LAM may result in lower risk of ADV resistance than ADV monotherapy.Other new drugs such as entecavir, telbivudine and tenofovir, are probably candidates for the treatment of hepatitis-B-surface-antigen-positive patients awaiting LT.After LT, low-dose intramuscular hepatitis B immunoglobulin(HBIG), in combination with LAM, has been regarded as the most cost-effective regimen for the prevention of post-transplant HBV recurrence in recipients without pretransplant LAM resistance and rapidly accepted in many transplant centers.With the introduction of new antiviral drugs, new hepatitis B vaccine and its new adjuvants, post-transplant HBIG-free therapeutic regimens with new oral antiviral drug combinations or active HBV vaccination combined with adjuvants will be promising, particularly in those patients with low risk of HBV recurrence.

Interferon alpha plus ribavirin combination treatment of Japanese chronic hepatitis C patients with HCV genotype 2:A project of the Kyushu University Liver Disease Study Group

AIM： To determine the efficacy of an interferon alpha and ribavirin combination treatment for Japanese patients infected with hepatitis C virus （HCV） of genotype 2, a multi-center study was retrospectively analyzed. METHODS： In total, 173 patients with HCV genotype 2 started to receive interferon-alpha subcutaneously thrice a week and 600-800 mg of ribavirin daily for 24 wk. RESULTS： The overall sustained virological response （SVR）, defined as undetectable HCV RNA in serum, 24 wk after the end of treatment, was remarkably high by 84.4%, （146/173） by an intention-to-treat analysis. A significant difference in SVR was found between patients with and without the discontinuation of ribavirin （46.9% vs 92.9 %）, but no difference was found between those with and without a dose reduction of ribavirin. A significant difference in SVR was also found between patients with less than 16 wk and patients with 16 or more weeks of ribavirin treatment （34.8 % vs 92.0 %）. CONCLUSION： The 24-wk interferon and ribavirin treatment is highly effective for Japanese patients with HCV genotype 2. The significant predictor of SVR is continuation of the ribavirin treatment for up to 16

Toxicological study of the hepatotherapeutic herbal formula,Chunggan extract,in beagle dogs

AIM: To evaluate the pharmaceutical safety of a Chinese herbal formula, Chunggan extract (CGX), traditionally prescribed as a hepatotherapeutic drug via systemic acute and subacute toxicological study. METHODS: Twenty male dogs and 20 female dogs were fed doses 50 times and 4 times greater than the clinically-recommended drug dosages in an acute and a subacute toxicological study, respectively. Adverse effects were examined by comparing the differences between normal and drug-administered groups using clinical signs, necropsies, histopathologic findings, haematology, urinalysis, and biochemical analysis. RESULTS: In the acute study no change in the body weight, diarrhoea, apetite, mortality rate and histopa- thology of major organs was observed in male or female dogs with a single administration of CGX at 5 g/kg. No drug-induced abnormalities at analysis of histopathology, haematology, urinalysis, and biochemistry were found with any dose of this drug. CONCLUSION: CGX is supposed to be very safe when used in a clinical application with a wide therapeutic index.

Diagnostic and therapeutic progress of multi-drug resistance with anti-HBV nucleos(t)ide analogues

Nucleos(t)ide analogues(NA) are a breakthrough in the treatment and management of chronic hepatitis B.NA could suppress the replication of hepatitis B virus(HBV) and control the progression of the disease.However,drug resistance caused by their long-term use becomes a practical problem,which influences the long-term outcomes in patients.Liver transplantation is the only choice for patients with HBV-related end-stage liver disease.But,the recurrence of HBV after transplantation often caused by the development of drug resistance leads to unfavorable outcomes for the recipients.Recently,the multi-drug resistance(MDR) has become a common issue raised due to the development and clinical application of a variety of NA.This may complicate the antiviral therapy and bring poorly prognostic outcomes.Although clinical evidence has suggested that combination therapy with different NA could effectively reduce the viral load in patients with MDR,the advent of new antiviral agents with high potency and high genetic barrier to resistance brings hope to antiviral therapy.The future of HBV researches relies on how toprevent the MDR occurrence and develop reasonable and effective treatment strategies.This review focuses on the diagnostic and therapeutic progress in MDR caused by the anti-HBV NA and describes some new research progress in this field.

Virological response to adefovir monotherapy and the risk of adefovir resistance

AIM:To evaluate virological response to adefovir(ADV) monotherapy and emergence of ADV-resistant mutations in lamivudine(LAM)-resistant chronic hepatitis B patients.METHODS:Seventy-seven patients with documented LAM resistance who were treated with 10 mg/d ADV for>96 wk were analyzed for ADV resistance.RESULTS:At week 48 and 96,eight(10%)and 14(18%)of 77 LAM-resistant patients developed the ADV-resistant strain(rtA181V/T and/or rtN236T mutations),respectively.Hepatitis B virus(HBV)DNA levels during therapy were significantly higher in patients who developed ADV resistance than in those who did not.Incidence of ADV resistance at week 96 was 11%,8%and 6%among patients with complete virological response(HBV DNA level<60 IU/mL);0%,5%and 19%among patients with partial virological response(HBV DNA level≥60 to 2000 IU/mL);and 32%,34% and 33%among patients with inadequate virological response(HBV DNA levels>2000 IU/mL)at week 12,week 24 and week 48,respectively.HBV DNA levels >2000 IU/mL at week 24 showed best performance characteristics in predicting ADV resistance.CONCLUSION:Development of ADV resistance mutations was associated with HBV DNA levels,which could identify patients with LAM resistance who are likely to respond to ADV monotherapy.

Recent Ⅳ-drug users with chronic hepatitis C can be efficiently treated with daily high dose induction therapy using consensus interferon:An open-label pilot study

AIM： To investigate the use of high dose consensusinterferon in combination with ribavirin in former iv drug users infected with hepatitis C. METHODS： We started, before pegylated （PEG）interferons were available, an open-label study to investigate the efficacy and tolerability of high dose induction therapy with consensus interferon （CIFN） and ribavirin in treatment of naiive patients with chronic hepatitis C. Fifty-eight patients who were former iv drug users, were enrolled receiving 18 μg of CIFN daily for 8 wk, followed by 9 μg daily for up to wk 24 or 48 and 800 mg of ribavirin daily. End point of the study was tolerability and eradication of the virus at wk 48 and sustained virological response at wk 72. RESULTS： More than 62% of patients responded to the treatment with CIFN at wk 24 or 48, respectively, showing a negative qualitative PCR [genotype 1 fourteen patients （56%）, genotype 2 five （50%）, genotype 3 thirteen （87%）, genotype 4 four （50%）]. Forty-eight percent of genotype 1 patients showed sustained virological response （SVR） six months after the treatment. CONCLUSION： CIFN on a daily basis is well tolerated and side effects like leuko- and thrombocytopenia are moderate. End of therapy （EOT） rates are slightly lower than the newer standard therapy with pegylated interferons. CIFN on a daily basis might be a favourable therapy regimen for patients with GTI and high viral load or for non-responders after failure of standard therapy.

Strategies for Antiviral Screening Targeting Early Steps of Virus Infection

Viral infection begins with the entry of the virus into the host target cell and initiates replication. For this reason, the virus entry machinery is an excellent target for antiviral therapeutics. In general, a virus life cycle includes several major steps: cell-surface attachment, entry, replication, assembly, and egress, while some viruses involve another stage called latency. The early steps of the virus life cycle include virus attachment, receptor binding, and entry. These steps involve the initial interactions between a virus and the host cell and thus are major determinants of the tropism of the virus infection, the nature of the virus replication, and the diseases resulting from the infection. Owing to the pathological importance of these early steps in the progress of viral infectious diseases, the development of inhibitors against these steps has been the focus of the pharmaceutical industry. In this review, Herpes Simplex Virus (HSV), Hepatitis C Virus (HCV), and Human Enterovirus 71 (EV71) were used as representatives of enveloped DNA, enveloped RNA, and non-enveloped viruses, respectively. The current mechanistic understanding of their attachment and entry, and the strategies for antagonist screenings are summarized herein.