Contamination of aflatoxins as threat to the safety of herbal Unani drugs: an overview

Unani medicine is an oldest system of traditional medicine,where drugs of animal,mineral and herbal origin are used for centuries to cure diseases.Unani remedies are now available not only in drug stores,but also in food stores and super markets.Therefore the efficacy and safety of these drugs is very crucial.One of the most serious risks associated with these remedies is,consumer assumes that they are natural,so they are safe.But biological contamination(bacterial,fungal and insect)of herbal medicines is a serious concern.The Aspergillus flavus and Aspergillus parasiticus are the fungal species that occur naturally,release aflatoxins and is a threat to the natural drugs.The World Health Organization has recommended determination of aflatoxins in natural drugs(Unani)as one of the parameter of their safety studies as Aflatoxin contamination is concerned significantly with health and economic loss affecting humans,animals,and agriculture.Aflatoxin B1 is categorized as a group 1 carcinogen by The International Agency for Research on Cancer that causes a variety of health issues.Thus keeping in mind the deleterious health effects of aflatoxins,here,in this review we have made an attempt to summarize the aflatoxins with respect to their origin,occurrence,structure and properties to generate the awareness among the people dealing mainly with Unani herbal drugs.Besides these their toxicity and effects on health have also been discussed.The analytical methods for their determination and some measures to prevent their contamination are also suggested to improve the efficacy and safety of Unani herbal drugs.

Follow-up Study of Retreatment TB Patients with Sputum Smear and/or Culture Positive Two Years after They were Declared Cured with First-line Anti-TB Drugs in Shandong Province

This study aimed to learn the recurrence rate in the retreatment TB patients with sputum smear and/or culture positive （ss＋ and/or c＋） two years after they were declared cured, and to explore causes of recurrence in order to improve long-time treatment outcome. 5 cities were selected as research locations. Recurrence of TB was judged by chest X-ray examination together with sputum smear and culture examination.

Exploring the compatibility theory of traditional Chinese medicine formulae:the disassembled prescriptions study

Traditional Chinese medicine(TCM)has become very popular in the treatment of complex diseases worldwide in recent decades.Despite the promising performance of TCM,how herbs work synergistically in a formula and their therapeutic targets remain ambiguous.This largely limits the correct use and modernization of TCM formulas clinically.The study of disassembled prescriptions is important for investigating the compatibility theory of Chinese medicines.By dissecting the mechanisms of TCM formulae,the compatibility principles of some well-known formulae,such as Realgar-Indigo naturalis,have been elucidated to a certain extent.In this review,several common methods of disassembled prescription studies are summarized,including those of single herb or mineral,sub-prescription,active ingredients or effective parts,large formulae,and systems pharmacology studies,as well as the methods of grouping based on the properties or efficacy of Chinese medicines,in order to provide evidence for formulae study.Moreover,some challenges to be addressed in disassembled prescriptions studies have been identified in this review.

Pretreatment and analysis techniques development of TKIs in biological samples for pharmacokinetic studies and therapeutic drug monitoring

Tyrosine kinase inhibitors(TKIs)have emerged as the first-line small molecule drugs in many cancer therapies,exerting their effects by impeding aberrant cell growth and proliferation through the modulation of tyrosine kinase-mediated signaling pathways.However,there exists a substantial inter-individual variability in the concentrations of certain TKIs and their metabolites,which may render patients with compromised immune function susceptible to diverse infections despite receiving theoretically efficacious anticancer treatments,alongside other potential side effects or adverse reactions.Therefore,an urgent need exists for an up-to-date review concerning the biological matrices relevant to bioanalysis and the sampling methods,clinical pharmacokinetics,and therapeutic drug monitoring of different TKIs.This paper provides a comprehensive overview of the advancements in pretreatment methods,such as protein precipitation(PPT),liquid-liquid extraction(LLE),solid-phase extraction(SPE),micro-SPE(μ-SPE),magnetic SPE(MSPE),and vortex-assisted dispersive SPE(VA-DSPE)achieved since 2017.It also highlights the latest analysis techniques such as newly developed high performance liquid chromatography(HPLC)and high-resolution mass spectrometry(HRMS)methods,capillary electrophoresis(CE),gas chromatography(GC),supercritical fluid chromatography(SFC)procedures,surface plasmon resonance(SPR)assays as well as novel nanoprobes-based biosensing techniques.In addition,a comparison is made between the advantages and disadvantages of different approaches while presenting critical challenges and prospects in pharmacokinetic studies and therapeutic drug monitoring.

The Assessment of the Clinical Effect of the Drug Compatibility and Course of Treatment to the Brucellar Spondylitis

Objective: To evaluate five drug treatment regimens in the treatment of Brucella spondylitis. Methods: Patients with clinical symptoms compatible and diagnostic test consistent with Brucella spondylitis were randomly assigned to five drug treatment regimens. Results: Combination therapy with doxycycline, rifampin and sulfamethoxazole for 56 consecutive days showed the highest cure rate of 20% after a single course and of 85% after a double course with affectivity rates of 55% and 95%. Cure rate and affectivity rate was significant better (P 0.05) than for patients receiving doxycycline, rifampin and streptomycin for the same period and regimens containing doxycycline were significant better than regimens without this drug. Conclusion: Combination therapy of doxycycline, rifampin and sulfamethoxazole for 8 weeks using one or two full courses should be recommended for Brucella spondylitis.

A qualitative study on the adverse reactions of mass treatment for lymphatic filariasis in Orissa,India

Objective:To describe the perceptions of community members and programme partners regarding severity,management and impact of adverse reactions on mass drug administration (MDA) compliance.Methods:Based on various qualitative data collected from five districts of Orissa,India,where MDA had been implemented during 2002 and 2004.The qualitative surveys included focus group discussions with community members and health workers,and semi-structured interviews with key informants in the community,medical officers at primary health centres,district level health officers and private practitioners.Results:It showed that many people suffered from adverse reactions,though the reactions were not serious.The paper reported different ways of management of adverse reactions at the community level.The impact of adverse reactions on MDA compliance was serious,as many people did not consume the drug due to fear of adverse reactions.The rumours of adverse reactions and news in media deterred people from consuming the tablets.Conclusion:All categories of respondents indicates the need of more information to address the problem of adverse reactions during MDA.The present paper warrants incorporating the messages on adverse reactions during health communication and social mobilization campaigns of MDA.

Study on Active Principle and Modernization of Chinese Drugs

The people as a whole cannot live for one day without drug, and the requirement of drugs would never come to an end or stay on the same level. Pharmaceutical industry, being of great significance, has become a new and important one in economic growth in the 21st century. Therefore, the modernization of Chinese drugs has also become a hot spot in public opinion in recent years.

A Clinical and Experimental Study on the Protective Effects of Jiangzhi Tongmai Fang on Endothelial Injury

31 cases of atherosclerosis (AS) were treated with Jiang Zhi Tong Mai Fang ([symbol: see text], formula of JZTMF), and its effect was compared with 30 cases treated with lovastatin in the control group. Clinically, the JZTMF formula showed an effect of regulating blood lipids, and therefore it was antiatherosclerotic. The mechanism is, probably, restoration of the function of endothelial cells (EC) by increasing the synthesis of 6-keto-PGF1 alpha and decreasing the release of endothelin (ET) as evidenced in the experimental study.

Enhancement of solubility and therapeutic potential of poorly soluble lovastatin by SMEDDS formulation adsorbed on directly compressed spray dried magnesium aluminometasilicate liquid loadable tablets: A study in diet induced hyperlipidemic rabbits

The aim of present study was to formulate and evaluate a self-microemulsifying drug delivery systems(SMEDDS)containing lovastatin and to further explore the ability of porous Neusilin■ US2 tablet as a solid carrier for SMEDDS.SMEDDS formulations of varying proportions of peceol,cremophor RH 40 and transcutol-P were selected and subjected to invitro evaluation,including dispersibility studies,droplet size,zeta potential measurement and release studies.The results indicated that the drug release profile of lovastatin from SMEDDS formulations was statistically significantly higher(p-value<0.05)than the plain lovastatin powder.Thermodynamic stability studies also confirmed the stability of the prepared SMEDDS formulations.The optimized formulation,which consists of 12% of peceol,44% of cremophor RH 40,and 44% of transcutol-P was loaded into directly compressed liquid loadable tablet of Neusilin■ US2 by simple adsorption method.In order to determine the ability of Neusilin®US2 as a suitable carrier pharmacodynamics study were also carried out in healthy diet induced hyperlipidemic rabbits.Animals were administered with both liquid SMEDDS and solid SMEDDS as well.From the results obtained,Neusilin■ was found to be a suitable carrier for SMEDDS and was equally effective in reducing the elevated lipid profile.In conclusion,liquid loadable tablet(LLT)is predicted to be a promising technique to deliver a liquid formulation in solid state.

The Role of Study Nurses in Clinical Trials of IBD Drugs

Objective: To explore the establishment and roles of study nurses in IBD drug clinical trials. Methods: The management experience of this department’s study nurses in IBD drug clinical trials was retrospectively analyzed. Results: The study nurses played very important roles at all links during the preliminary preparation of IBD drug clinical trials, the whole-process management after project initiation, and the later work of project conclusion. Conclusions: As direct participants in drug clinical trials, study nurses play a very important role in ensuring standardization of the trial process, safeguarding patient’s rights and safety, and assisting investigators in carrying out study works smoothly.

PREDICTION OF THE THERAPEUTIC EFFECTIVENESS OF NEW DRUGS FROM CLINICAL PHARMACOLOGY STUDIES

The development of new drugs for therapeutic purposes has become very expensive and time-consuming in American and European countries.It is estimated that on the average 50 to 100 million dollars and 10 or more years from the time of patenting are required to make a new drug available for general prescription. Every new drug needs to be charac-

Some Hot Spots in the Study of Chinese Drugs in the 21st Century

Mankind has entered the 21st century of high speed development in science and e-conomics. Owing to the alteration of disease modes in the new century, the greatly elevated quality of human life and the arrival of aged society, the modes of medicine have obviously changed from the treatment mode

Clinical Observation on the Method of Supplementing Qi,Clearing away Heat and Promoting Blood Circulation for Treating 53 Cases of Gastritis Related to Pyrolic Helicobacterium

According to the clinical experience of professor Shan Zhaowei (单兆伟), the author has successfully developed Qingyou Yangwei Capsule (清幽养胃胶囊capsules for eliminating pyrolic Helicobacterium and nourishing the stomach) for treating the gastritis. Clinical research has shown that the capsule has a good curative effect on chronic gastritis related to pyrolic Helicobacterium. Among the 53 cases in the treatment group, clinical observation showed cure in 6 cases, obvious effect in 18 cases, effect in 24 cases, no effect on 5 cases, with a total effective rate of 90.5%. Of the 50 cases in the control group, cure was found in 5 cases, obvious effect in 13 cases, effect in 20 cases, no effect in 12 cases, the total effective rate being 76%. The total effective rate in the treatment group was higher than that in the control group. The rate of eliminating pyrolic Helicobacterium in the treatment group was 66.04%, similar to that in the control group. In a follow-up visit 6 months later, the recurrence rate in the treatment group was 13.33%, obviously lower than that of 41.66% in the control group.

Association between Maternal Drug Use and Cytochrome P450 Genetic Polymorphisms and the Risk of Congenital Heart Defects in Offspring

Objective This study aimed to assess the associations between maternal drug use,cytochrome P450(CYP450)genetic polymorphisms,and their interactions with the risk of congenital heart defects(CHDs)in offspring.Methods A case-control study involving 569 mothers of CHD cases and 652 controls was conducted from November 2017 to January 2020.Results After adjusting for potential confounding factors,the results show that mothers who used ovulatory drugs(adjusted odds ratio[a OR]=2.12;95% confidence interval[CI]:1.08-4.16),antidepressants(a OR=2.56;95%CI:1.36-4.82),antiabortifacients(a OR=1.55;95%CI:1.00-2.40),or traditional Chinese drugs(a OR=1.97;95%CI:1.26-3.09)during pregnancy were at a significantly higher risk of CHDs in offspring.Maternal CYP450 genetic polymorphisms at rs1065852(A/T vs.A/A:OR=1.53,95%CI:1.10-2.14;T/T vs.A/A:OR=1.57,95%CI:1.07-2.31)and rs16947(G/G vs.C/C:OR=3.41,95%CI:1.82-6.39)were also significantly associated with the risk of CHDs in offspring.Additionally,significant interactions were observed between the CYP450 genetic variants and drug use on the development of CHDs.Conclusions In those of Chinese descent,ovulatory drugs,antidepressants,antiabortifacients,and traditional Chinese medicines may be associated with the risk of CHDs in offspring.Maternal CYP450 genes may regulate the effects of maternal drug exposure on fetal heart development.

Modern drug discovery for inflammatory bowel disease: The role of computational methods

Inflammatory bowel diseases(IBDs)comprising ulcerative colitis,Crohn’s disease and microscopic colitis are characterized by chronic inflammation of the gastrointestinal tract.IBD has spread around the world and is becoming more prevalent at an alarming rate in developing countries whose societies have become more westernized.Cell therapy,intestinal microecology,apheresis therapy,exosome therapy and small molecules are emerging therapeutic options for IBD.Currently,it is thought that low-molecular-mass substances with good oral bio-availability and the ability to permeate the cell membrane to regulate the action of elements of the inflammatory signaling pathway are effective therapeutic options for the treatment of IBD.Several small molecule inhibitors are being developed as a promising alternative for IBD therapy.The use of highly efficient and time-saving techniques,such as computational methods,is still a viable option for the development of these small molecule drugs.The computeraided(in silico)discovery approach is one drug development technique that has mostly proven efficacy.Computational approaches when combined with traditional drug development methodology dramatically boost the likelihood of drug discovery in a sustainable and cost-effective manner.This review focuses on the modern drug discovery approaches for the design of novel IBD drugs with an emphasis on the role of computational methods.Some computational approaches to IBD genomic studies,target identification,and virtual screening for the discovery of new drugs and in the repurposing of existing drugs are discussed.

Low eradication rate of Helicobacterpyloriwith triple 7-14 days and quadriple therapy in Turkey

AIM:The eradication rate of Helicobacter pylori (H pylori) shows variation among countries and regimens of treatment. We aimed to study the eradication rates of different regimens in our region and some factors affecting the rate of eradication. METHODS:One hundred and sixty-four H pylori positive patients (68 males,96 females;mean age:48±12 years) with duodenal or gastric ulcer without a smoking history were included in the study.The patients were divided into three groups according to the treatment regimens.Omeprazole 20mg,clarithromycin 500mg,amoxicillin 1g were given twice daily for 1 week (Group Ⅰ) and 2 weeks (Group Ⅱ). Patients in Group Ⅲ received bismuth subsitrate 300mg, tetracyline 500mg and metronidazole 500mg four times daily in addition to Omeprazole 20mg twice daily.Two biopsies each before and after treatment were obtained from antrum and corpus,and histopathologically evaluated. Eradication was assumed to be successful if no H pylorus was detected from four biopsy specimens taken after treatment.The effects of factors like age,sex,H pylori density on antrum and corpus before treatment,the total H pylori density,and the inflammation scores on the rate of H pylori eradication were evaluated. RESULTS:The overall eradication rate was 42%.The rates in groups Ⅱ and Ⅲ were statistically higher than that in group Ⅰ (P<0.05).The rates of eradication were 24.5%, 40.7% and 61.5% in groups Ⅰ,Ⅱ and Ⅲ,respectively.The eradication rate was negatively related to either corpus H pylori density or total H pylori density (P<0.05).The median age was older in the group in which the eradication failed in comparison to that with successful eradication (55 yr vs 39 yr,P<0.001).No correlation between sex and H pylori eradication was found. CONCLUSION:Our rates of eradication were significantly lower when compared to those reported in literature.We believe that advanced age and high H pylori density are negative predictive factors for the rate of H pylori eradication.

THERAPEUTIC EFFECTS OF THE COMBINED CHINESE AND WESTERN MEDICINE ON METASTATIC CARCINOMA IN THE SUPRACLAVICULAR LYMPH NODES——An Analysis of 285 Cases

Between 1985 and 1989, 285 cases of metastatic carcinoma in the supraclavicular lymph nodes were treated by the following five methods: Chinese medication, radiotherapy plus Chinese medication, chemotherapy plus Chinese medication, combined Chinese and Western medicine and expectant treatment. Analysis shows that radiotherapy plus Chinese medication has the best curative effect with an effective rate of 75.5%. The effective rates were 74.2% for the combined treatment, 55.5% for the chemotherapy plus medication, 12.5% for the Chinese medication, and none for expectant treatment.

Estimation of Metformin Drug for the Diabetes Patients by Simple,Quick and Cheap Techniques within the Formation of Colored Charge Transfer Complexes

Metformin(Met)is a drug developed for the treatment of patients with typeⅡ diabetes.Recently,Met estimation in pharmaceutical formulations and human fluids has gained a growing interest.To extend requisite data that can be used to assessment of Met quantitatively based on charge-transfer(CT)complexation,the present study describes the synthesis and characterization of CT complexes that formed between drug Met and the organicπ-acceptors picric acid(PA),chloranilic acid(CLA),chloranil(CHL),7,7',8,8'-tetracyanoquinodimethane(TCNQ),and dichlorodicyanobenzoquinone(DDQ).The properties of the formed CT complexes were investigated by elemental,spectral(UV-visible,IR,and Raman spectroscopies),thermal(TG)and morphological(SEM)studies.IR results indicated that the complexation of Met with either PA or CLA acceptors occurs through proton transfer interaction,whereas its complexation with CHL,TCNQ,or DDQ acceptors occurs through n→π*interaction.

Epidemiological Investigation of Brucellosis Spondylitis and Optimal Selection of Clinical Drug Compatibility, Treatment Course and Treatment Plan

Background: Brucellosis is a zoonotic endemic disease, the main source of infection is infected cattle, sheep, pigs and their products. In recent years, the global incidence of brucellosis spondylitis has increased year by year, and it has spread from pastoral areas to semi-agricultural and semi-pastoral areas, agricultural areas and cities. It has changed from a mainly occupational disease to a mainly food-borne disease, and it is also a zoonotic specific spinal infectious disease that WHO and governments around the world pay great attention to. Due to the low cure rate and high recurrence rate of traditional drug therapy regimen. Therefore, to carry out epidemiological investigation and Related research on clinical drug therapy of brucellosis spondylitis has practical significance for improving diagnosis rate, cure rate and reducing recurrence rate. Objective: To analyze the epidemiological characteristics of Brucellosis spondylitis and explore the choice of drugs and the best drug treatment plan, so as to provide scientific basis for improving the prevention and control of the disease and treatment effect. Methods: Clinical epidemiodogical materials were collected from 113 patients with brucellar spondylitis. All these patients were divided into 5 different groups according to 5 kinds of drugs adopted respectively, and then the patients were given different course of treatment. Results: In the 113 patients, brucellar spondylitis morbility of female patients were higher than that of male ones, and the morbility of Bashang were higher than that of Baxia. These patients were infected mainly through browsing and breeding beasts. Lumbars were the major focus of infection. It was very comnlon that two adjacent lumbars were involved in concurrently. L4 was the most common infection location and its demolishment was most serious. The curative effect of group treated with doxycycline was better than that of group treated without doxycycline. If the course of treatment Was increased, the curative effect Was not increased obviously. Conclusions: There are characteristic features in clinical epidemiology of brucell spondylitis. Doxycycline + Rifampicin + Sulfamethoxazole was used as the preferred antibiotic. Using antibiotics adequately and jointly by two courses of treatment for a long time is the most reasonable way to treat the disease and prevent the disease from recurrence.

Analysis on Common Compatibility Contraindications of Breviscapine for Injection

[Objectives]To analyze the common compatibility contraindications of breviscapine for injection,and to provide references for clinical rational drug use.[Methods]The pH distribution of the combined drugs in the report on the compatibility contraindications of breviscapine for injection and was analyzed.[Results]Breviscapine for injection may become turbid or precipitated when mixed with drugs whose pH are lower;it can make the liquid discoloration in a strong alkaline solution.[Conclusions]Breviscapine for injection should not be combined with drugs whose pH are lower,especially drugs with pH lower than 4.2.Breviscapine for injection should not be used with drugs with strong alkaline.It is recommended to use Breviscapine for injection separately.