Medicinal Drug Use Research Articles

Extended withdrawal time (EWDT) of drugs to prevent residues in food following extra label use

Safety of food originated from animals is an emerging global health problem, and ensuring food safety is a challenge for the producers and governments who deal with protecting the food supply chain from contamination with hazardous microbes, chemicals and/or drugs. In the United States (US), the Food Animal Residue Avoidance Databank (FARAD) program is a unique consortium of scientific experts who help maintain a proper balance among animal health, food safety, and regulatory policies. Veterinarians must often use drugs in an extra-label manner to treat food animals due to limited availability of Food and Drug Administration (FDA) approved drugs. Extra-label drug use (ELDU) is allowable under the Animal Medicinal Drug Use Clarification Act (AMDUCA). Following ELDU, and before products derived from the treated animal can be sold and marketed, an extended withdrawal time (EWDT) needs to be established, based on appropriate scientific data. The objective of this paper is to discuss the scientific basis for determination of EWDT of drugs used in food animals using kinetic modeling approach.

Burnout, associated comorbidities and coping strategies in French community pharmacies-BOP study: A nationwide cross-sectional study.

BackgroundWork-related stress and burnout syndromes are unfortunately common comorbidities found in health professionals. However, burnout syndrome has only been partly and episodically assessed for community pharmacists whereas these professionals are exposed to patients’ demands and difficulties every day. Prevalence of burnout, associated comorbidities and coping strategies were assessed in pharmacy teams (pharmacists and pharmacy technicians) in French community pharmacies.MethodsThis online survey was performed by emails sent to all French community pharmacies over 3 months. The survey assessed the prevalence of burnout (Maslach Burnout Inventory—MBI—questionnaire), anxiety, depression and strategies for coping with work-related stress.ResultsOf the 1,339 questionnaires received, 1,322 were completed and useable for the analysis. Burnout syndrome was detected in 56.2% of respondents and 10.5% of them presented severe burnout syndrome. Severe burnout syndrome was significantly associated with men, large urban areas and the number of hours worked. Depression and anxiety were found in 15.7% and 42.4% of respondents, respectively. These co-morbidities were significantly associated with severe burnout syndrome. Higher MBI scores were significantly associated with medical consultations and medicinal drug use. Conversely, respondents suffering from burnout syndrome declared they resorted less to non-medical strategies to manage their work-related stress (leisure, psychotherapy, holidays and time off).ConclusionThis study demonstrated that community pharmacists and pharmacy technicians presented high prevalence of burnout syndrome, such as many healthcare professionals. Unfortunately, burnout syndrome was associated with several comorbidities (anxiety, depression and alcohol abuse) and the consumption of health resources. The psychological suffering of these healthcare professionals underlines the necessity to deploy a strategy to detect and manage burnout in community pharmacy.

Prescription medicine use by pedestrians and the risk of injurious road traffic crashes: A case-crossover study.

BackgroundWhile some medicinal drugs have been found to affect driving ability, no study has investigated whether a relationship exists between these medicines and crashes involving pedestrians. The aim of this study was to explore the association between the use of medicinal drugs and the risk of being involved in a road traffic crash as a pedestrian.Methods and findingsData from 3 French nationwide databases were matched. We used the case-crossover design to control for time-invariant factors by using each case as its own control. To perform multivariable analysis and limit false-positive results, we implemented a bootstrap version of Lasso. To avoid the effect of unmeasured time-varying factors, we varied the length of the washout period from 30 to 119 days before the crash. The matching procedure led to the inclusion of 16,458 pedestrians involved in an injurious road traffic crash from 1 July 2005 to 31 December 2011. We found 48 medicine classes with a positive association with the risk of crash, with median odds ratios ranging from 1.12 to 2.98. Among these, benzodiazepines and benzodiazepine-related drugs, antihistamines, and anti-inflammatory and antirheumatic drugs were among the 10 medicines most consumed by the 16,458 pedestrians. Study limitations included slight overrepresentation of pedestrians injured in more severe crashes, lack of information about self-medication and the use of over-the-counter drugs, and lack of data on amount of walking.ConclusionsTherapeutic classes already identified as impacting the ability to drive, such as benzodiazepines and antihistamines, are also associated with an increased risk of pedestrians being involved in a road traffic crash. This study on pedestrians highlights the necessity of improving awareness of the effect of these medicines on this category of road user.

Metronidazole for the treatment ofTritrichomonas foetusin bulls

BackgroundTritrichomonas foetusis a sexually transmitted protozoon that causes reproductive failure, among cattle, so disruptive that many western US states have initiated control programs. Current control programs are based on the testing and exclusion of individual bulls. Unfortunately, these programs are utilizing screening tests that are lacking in sensitivity. Blanket treatment of all the exposed bulls and adequate sexual rest for the exposed cows could provide a more viable disease control option. The objectives of this study were twofold. The first objective was to demonstrate effectiveness for metronidazole treatment of a bull under ideal conditions and with an optimized treatment regime. This type of study with a single subject is often referred to as an n-of-1 or single subject clinical trial. The second objective of the current study was to review the scientific basis for the banning of metronidazole for use in Food Animals by the Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA).ResultsResults from an antimicrobial assay indicated that metronidazole at a concentration of 0.5 μg/mL successfully eliminated in vitro protozoal growth of bovineTritrichomonas foetus.The estimated effective intravenous dose was two treatments with 60 mg/kg metronidazole, 24 h apart. A bull that had tested positive forTritrichomonas foetusculture at weekly intervals for 5 weeks prior to treatment was negative forTritrichomonas foetusculture at weekly intervals for five consecutive weeks following this treatment regimen. An objective evaluation of the published evidence on the potential public health significance of using metronidazole to treatTritrichomonas foetusin bulls provides encouragement for veterinarians and regulators to consider approaches that might lead to permitting the legal use of metronidazole in bulls.ConclusionThe study demonstrated successful inhibition of Tritrichomonas foetusboth in vitro and in vivo with metronidazole. The current status of metronidazole is that the Animal Medicinal Drug Use Clarification Act of 1994 prohibits its extra-label use in food-producing animals. Veterinarians and regulators should consider approaches that might lead to permitting the legal use of metronidazole in bulls.

English

The aim of this study was to evaluate the prevalence of the concomitant use of herbal medicine and anti-retroviral drugs in people living with HIV/AIDs and to evaluate the reasons given by the patients for concomitant administration of highly active antiretroviral therapy (HAART) with herbal drugs in order to establish a possible link between the use of herbal medicines and adherence. A cross sectional study design was utilized via systematic sampling for recruitment of HIV positive individuals receiving their medications in Amuwo-Odofin and Ojo areas in Lagos, Nigeria. Based on the inclusion criteria, 351 HIV positive patients were recruited into the study from the HIV outpatient clinics of two hospitals and had the questionnaires administered to them. 42.7% of the respondents stated that they use herbal medicines. The association for each of the herbal medicines with side effects experienced with the use of ARVs was statistically significant upon cross-tabulation and was a major predictor of herbal drug use. The prevalence of herbal drug use in patients who were adhering to HAART medication was not significantly different from those who were not adhering to medication (p = 0.75 and χ2 = 6.902). The use or lack of use of herbal medicine is not a determinant for adherence. The most profound reason for herb use was to improve treatment. However, herb/drug interaction studies are imperative to ascertain if interactions occurring are beneficial or harmful. The pharmacist must counsel and re-counsel patients on HAART, not to use herbal products with their antiretroviral medications to avoid drug-herb interactions which could be potentially life threatening. Key words: Highly active antiretroviral therapy (HAART), herbal drugs, adherence.

Illicit Drugs among Crashed Drivers, A First Toxicological Investigation in Albania

This study aims to investigate the presence of drugs in this group of drivers who already had a crash (injured or killed drivers). By law, the prosecutor is the authority who requests the toxicological examination specifying the type of analysis that will be performed, usually only alcohol test is required. There has been some investigation regarding the influence of alcohol in traffic crashes in Albania (3,190,089 inhabitants), but never a research regarding the use of illicit and medicinal drugs in drivers in our country. Alcohol was analyzed in blood by head-space gaschromatography. Blood samples were also screened for psychoactive substances (opiates, cocaine metabolites, cannabis, amphetamines, methamphetamines, benzodiazepines, tricyclic antidepressants, barbiturates) by immunological methods. Their presence was confirmed by gas-chromatography. Overall, 82 car drivers were included in the study. Drivers involved in accidents were more frequently men 98.8% (n=81). 46 drivers (56.1%) had a positive blood alcohol concentration at the time of the crash, but only 23 (28%) had toxic concentrations exceeding 1.2 g/l. In total, 15.9% were positive for illicit drugs and medicinal drugs. This study revealed that beside alcohol, psychoactive substances were present in Albanian crashed drivers, too.

Prospects of using melatonin in the reproductive medicine

Studies in recent decades have greatly expanded understanding of the role of melatonin in the human organism, showing that its functions extend well beyond the regulation of the sleep-wake rhythms. The article describes the results of studies about role of the epiphyseal and non-epiphyseal melatonin in various processes occurring in the implementation of the human reproductive function, and analyzed of the prospects for the use of melatonin drugs in reproductive medicine and gynecology.As numerous studies is showed, melatonin has an important integrating multifaceted role in regulation of the human reproduction. In particular, in addition to protective effects, melatonin has a direct impact on the growth and maturation of oocytes, as well as increases the level of fertilization. One of studies shows, what the application of melatonin (3 mg per day for 2 weeks) for women with low fertilization level in program of assisted reproductive technology (ART), was increased this level in the next cycle from 35.1 to 68.2%, and the number of high quality embryos was increased from 48 to 65.6%. The study authors conclude that the use of melatonin in ART cycles has a positive effect on cycles efficiency by reducing the damaging effects of oxidative stress on oocyte.Furthermore, melatonin, which toxicity is extremely low, well penetrates through the hematotesticular barrier, which makes its use promising in the treatment of male infertility with ART. Studies by various authors convincingly demonstrate the protective effect of melatonin against the damaging effects of oxidative stress, which is accompanied by a manipulation with ejaculate as part of ART.One of reviews in 2016 was analyzed all available literature data on safety of melatonin drugs. The results showed that short-term use of melatonin is safe even in extreme doses. None of the studies not reported about serious side effects. Among minor effects were observed dizziness, nausea, headache, drowsiness. The data indicate that the scope of clinical application of melatonin is not limited to the timing rhythms sleep-wake: its powerful antioxidant effects are universal and can be used in a treatment of variety of pathologies, including reproductive disorders in women and men.

Possibility of potential herbal-drug interactions in elderly population

Medicines are variable in composition and quality, which may have an impact on their interaction profile still as a result of the reliability of reports regarding them. As such, the potential for herb-drug interactions increases in elderly population. For this instance we conducted a survey based study in which 208 patients were surveyed belonging to different areas of Karachi. These people were of different age groups ranging from 40-60 years old. They were asked to answer a face to face questionnaire based on the concurrent use of the conventional medicine and herbal drugs and their possible interaction based side effects. Our results sho ws that out of 208, 124(59.6%) volunteers prefer treatment with herbal and allopathic medicines, 138 (66.3%) use medications on daily basis while 70 (33.7%) don’t use on daily basis. And 56 volunteers were at high risk of potential herb-drug interaction, among them 32.7% have dynamic interactions and 21.2% have kinetic interactions in their medication regime. Out of 208 volunteers 89% were experiencing adverse effects (self reported). Since a significant number of herb-drug interactions were detected in elderly patients, it is suggested that health care professionals and consumers should be aware of the potential herb-drug interactions and health care professionals should question and advice their patients on their use of herbal medicines.

The association between alcohol, medicinal drug use and post-traumatic stress symptoms among Norwegian rescue workers after the 22 July twin terror attacks

BackgroundThe aim of this study was to assess whether the use of alcohol and medicinal drugs among rescue workers as a consequence of the 22 July terrorist attack was associated with post-traumatic stress symptoms, and explore if there were differences between affiliated and unaffiliated rescue workers. MethodsTen months after the bombing in the Oslo government district and the shooting at the youth camp on Utøya Island, a cross-sectional study of 1790 rescue and healthcare workers was conducted. The questionnaire included information on medicinal drug and alcohol use, experiences during rescue work and PTSS. ResultsFew rescue workers reported alcohol (6.8% n = 119) or medicinal drug (5.5% n = 95) use as a consequence of participation in the 22 July terror attacks. Alcohol and medicinal drug use was associated with an elevated level of PTSS among the rescue workers who reported to use medicinal drugs (11.1 95% CI: 5.7–21.8) or alcohol (10.0 95% CI: 5.2–19.0) as a consequence of the terror attacks. ConclusionThe study found a low level of post-traumatic stress symptoms (PTSS) and alcohol and medicinal drug use among the rescue workers after the terror attacks in Norway on 22 July 2011. There was a strong association between both medicinal drug and alcohol use and elevated PTSS.

The use of Chinese herbal drugs in Islamic medicine

This paper investigates some of the ways that Chinese medicine has been transferred to the Western world and to Islamic territories. During the Golden Age of Islam (8th to 13th century CE), the herbal drug trade promoted significant commercial and scientific exchange between China and the Muslim world. Chinese herbal drugs have been described by medieval Muslim medical scholars such as Tabari (870 CE), Rhazes (925 CE), Haly Abbas (982 CE), Avicenna (1037 CE) and Jurjani (1137 CE). The term al-sin (the Arabic word for China) is used 46 times in Avicenna's Canon of Medicine in reference to herbal drugs imported from China. Cinnamon (dar sini; “Chinese herb”), wild ginger (asaron), rhubarb (rivand-e sini), nutmeg (basbasa), incense tree wood (ood), cubeb (kababe) and sandalwood (sandal) were the most frequently mentioned Chinese herbs in Islamic medical books. There are also multiple similarities between the clinical uses of these herbs in both medical systems. It appears that Chinese herbal drugs were a major component of the exchange of goods and knowledge between China and the Islamic and later to the Western world amid this era.

Antibacterial Effects of Herbal Compounds against Acinetobacter baumannii Isolated from Hospital of Tehran, Iran

ncreasing isolation of multidrug-resistant Acinetobacter baumannii (MDR) has been reported in worldwide and it is recently one of the most difficult nosocomial acquired gram-negative pathogens to control and treatment. These bacteria are one of ESBL producing that great potential have for the rapid development of antibiotic resistance. Use of medicinal herbaceous drugs recommended for treatment since ancient periods. Humans have been used and realize their beneficial effects. With the increase in population and urban growth, reduced use of synthetic drugs, many of these of medicinal herbs have been replaced. Because of Satureja, Origanum vulgare and Thyme essence has antimicrobial properties so can be used against infections caused by MDR Acinetobacter baumannii

Evaluation of rational use of veterinary drugs especially antimicrobials and anthelmintics in Bishoftu, Central Ethiopia.

BackgroundRational use of drugs in veterinary medicine has numerous benefits, such as increasing efficacy, decreasing the potential adverse effects, reducing risk of drug residue and combating development of microorganism’s drug resistance.MethodsA retrospective study with the aim of evaluating the current rational use of veterinary drugs was conducted at college of veterinary medicine and agriculture veterinary teaching hospital and Ada district veterinary clinic, central Ethiopia. One thousand eight hundred and nineteen animal patients’ encounters were randomly selected for the study from prescription papers and prescription registration books retrospectively.ResultsThe average number of drugs prescribed per encounter was 1.23 with maximum of five. The percentage of encounters in which antimicrobials and anthelmintics was prescribed were 54.4 % (1216/2235) and 38.9 % (869/2235), respectively. The percentages of drugs prescribed by generic name and from essential veterinary drug list were 90.1 % (2014/2235) and 99.7 % (2229/2235), respectively. The most commonly prescribed antimicrobials and anthelmintics were oxytetracycline 1016 (45.5 %), penicillin and streptomycin combination 168 (7.5 %), sulfa drugs 23 (1.0 %), and albendazole 732 (32.8 %) and ivermectin 137 (6.1 %). Among the 1819 animal-patient encounters, only 57 % (n = 1037) of the prescriptions were written adequately, 43 % (n = 782) incorrectly prescribed and 1179 cases of the adequately specified prescription were tentatively diagnosed. For 656 (53.9 %) and 233 (26.8 %) inadequately specified cases antimicrobials and anthelmintics were prescribed, respectively. Antibiotics were prescribed irrationally for cases which were tentatively diagnosed as parasitic 21.6 % (n = 262) and viral to prevent secondary bacterial complications 6.0 % (n = 73). Among all patients that were admitted to veterinary clinics, 96.6 % (1757) were treated empirically without getting correct laboratory-supported diagnosis. Chi Square test for trend analysis showed a statistically significant association between irrational drug usage and year (p = 0.000).ConclusionsThe findings had shown problems in generic prescribing, incorrect diagnosis, and non-availability of standard veterinary treatment guideline and drug formulary in the study area. Therefore, veterinary drugs, specially, antimicrobial agents should be judiciously used; and a wide scale study to safeguard the public from drug residual effects and antimicrobial resistance development is recommended.

Traditionelle chinesische Arzneitherapie bei Patienten mit chronischer Rhinosinusitis − eine Therapiebeobachtung mit Berücksichtigung der Arzneimittelherkunft

Hintergrund: Chinesische Arzneimittel werden in Deutschland zunehmend angewandt. Der Import erfolgt primär aus China, mit der Folge einer erschwerten Qualitätskontrolle und Gewährleistung der Therapiesicherheit. Aus diesem Grund werden wichtige chinesische Arzneipflanzen seit 1999 in einem interdisziplinären Forschungsprojekt von der Bayerischen Landesanstalt für Landwirtschaft kontrolliert angebaut und wissenschaftlich erforscht, mit inzwischen bereits 16 «bayerischen Arzneidrogen», die in der lokalen Versorgung verwendet und über Apotheken abgegeben werden. Trotz vergleichbarer Qualität gibt es Vorbehalte, denn die bayerischen Arzneimittel werden seit 2006 in Deutschland eingesetzt, ohne dass die Wirksamkeit im Vergleich zu den chinesischen Arzneimitteln untersucht wurde. Aus diesem Grund führten wir eine Therapiebeobachtung mit einem Parallelgruppendesign bei Patienten mit chronischer Rhinosinusitis durch. Methodik: Die Beobachtungsdauer betrug 4 Wochen. Nach einem 4-wöchigen Follow-up wurden die Patienten nochmals telefonisch befragt. Während der Therapiebeobachtung nahmen die Patienten täglich 2 × 50 ml eines Dekokts aus chinesischen Arzneimitteln entweder (a) überwiegend aus bayerischem kontrolliertem Versuchsanbau (Bayern-Gruppe) oder (b) rein chinesischer Handelsware (China-Gruppe) zu sich. Die Bewertung des Therapieerfolgs erfolgte durch Numerische Rating-Skalen. Ergebnisse: Insgesamt beendeten 64 Patienten die Therapiebeobachtung (31 Bayern-Gruppe, 33 China-Gruppe). In beiden Gruppen zeigten sich deutliche Verbesserungen in den Hauptsymptomen der chronischen Rhinosinusitis wie auch in den Nebensymptomen wie Infektneigung und allgemeiner Gesundheitszustand. Zwischen den Gruppen gab es keine relevanten Unterschiede bei der Besserung der Hauptsymptome. Die Dekokte waren insgesamt gut verträglich, schwere Nebenwirkungen traten nicht auf. Schlussfolgerung: Chinesische Arzneimittel aus bayerischem Anbau waren in dieser Beobachtungsstudie ähnlich wirksam wie Arzneikräuter aus China, allerdings müssen auch die Effekte der Begleittherapie, insbesondere der Akupunktur berücksichtigt werden. Die Veränderung der Symptome während der Behandlungszeit sollte zu weiteren Studien Anlass geben, die die Wirksamkeit dieser Arzneimittelrezeptur bei chronischer Rhinosinusitis untersuchen.

Antiviral chemotherapy in veterinary medicine: current applications and perspectives.

The current situation in the use of antiviral drugs in veterinary medicine is characterised by a novel and optimistic approach.Viruses of veterinary importance are still used as animal models in the developmentof human therapeutics, but there is growing interest in many of these viruses in the identification of antiviral molecules for use in both livestock and companion animals. The use of antiviral drugs in livestock animals is envisaged for the treatment or control of disease on a large scale (mass treatment), whereas in companion animals an individual approach is favoured. An overview of the most recent examples of research in the use of antivirals in veterinary medicine is presented, with particular emphasis on their in vivo applications.

Which drugs are associated with highest risk for being arrested for driving under the influence? A case–control study

The aim of this study was to determine the association between drug type and arrest for driving under the influence of drugs (DUID) by calculating odds ratios (ORs) using a case–control design. A DUID arrest is in most cases related to aberrant or risky driving and might therefore be regarded as a proxy for a drug related traffic crash. The ‘cases’ were 2738 drivers arrested on suspicion of drugged driving from April 2008 to March 2009 with blood alcohol concentrations below the legal limit of 0.2g/L; 794 were arrested due to involvement in road traffic crashes, whereas 1944 were arrested for other reasons, mainly dangerous driving, suspected impairment when stopped in traffic controls, or because of phone calls to the police from other road users or observers. The ‘controls’ were 9375 random drivers in normal traffic, also with alcohol concentrations below this limit. Blood samples from ‘cases’ and oral fluid samples from ‘controls’ were analyzed for 15 drugs that have legislative concentration limits in Norway, in addition to two other commonly detected psychoactive drugs. The most prevalent illicit drug in the control group was tetrahydrocannabinol (THC; 0.58%), which was also commonly found in samples from drivers arrested due to road crash (15.6%) or arrested for other reasons (21.8%). Amphetamine/methamphetamine was most prevalent among arrested drivers involved in crashes (30.6%) and drivers arrested for other reasons (56.9%), whereas only 0.18% of the control group was positive for amphetamine/methamphetamine. The single-use substances which gave highest OR for police arrest were amphetamine/methamphetamine, alprazolam, clonazepam and oxazepam. The majority of the alprazolam and clonazepam findings were probably due to non-therapeutic use of medicinal drugs purchased on the illegal market. Combinations of two or more drugs yielded higher ORs than the use of single substances; combinations of amphetamine/methamphetamine and benzodiazepines gave the highest risk.

A comparison of alcohol and drug use by random motor vehicle drivers in Brazil and Norway

BackgroundA large proportion of road traffic crashes are related to driving under the influence (DUI) of alcohol or drugs. The aim of this study was to compare the use of alcohol, illegal drugs and psychoactive medicinal drugs among random drivers in Brazil and Norway, two countries with the same legal limit for drunk driving, but with marked differences in legislation history, enforcement and penalties for DUI, and to discuss any differences found. MethodsRoadside surveys were conducted on Fridays and Saturdays between noon and midnight. Samples of oral fluid were collected for analysis of drugs, whereas alcohol was determined by breath testing or by analysis of oral fluid. ResultsHigh participation rates of 94–97% were obtained in both countries. The weighted prevalence of driving with alcohol concentrations in breath or oral fluid equivalent to blood alcohol concentrations (BAC) above 0.2g/L was 2.7% (95% CI 2.2–3.3) in Brazil and 0.2% (95% CI 0.0–0.5) in Norway. Stimulants (amphetamines or cocaine) were found in samples from 1.0% (95% CI 0.7–1.4) of drivers in Brazil and 0.3% (95% CI 0.1–0.7) in Norway. The prevalence of amphetamines was highest among Brazilian truck drivers (3.6%; 95% CI 2.0–6.4). Tetrahydrocannabinol was found in samples from 0.5% (95% CI 0.3–0.8) of drivers in Brazil and 1.0% (95% CI 0.6–1.5) in Norway, whereas benzodiazepines or zopiclone were found in 1.0% (95% CI 0.7–1.4) and 1.7% (95% CI 1.2–2.4) of the samples from Brazil and Norway, respectively. ConclusionsThe difference in the prevalence of alcohol may be related to the fact that Norway has implemented steps to reduce drunk driving since 1936, whereas Brazil has attempted to do the same for only a few years. Differences for drugs may be related to different patterns in the use of stimulants, cannabis and medicines.

Andrographia paniculata a Miracle Herbs for cancer treatment: In vivo and in vitro studies against Aflatoxin B1 Toxicity

BackgroundThe history of natural products used in ancient times and in folk medicine these days, around the world, is the basis for the use of many therapeutic drugs in modern day medicine. Andrographia paniculata belongs to the family Acanthaceae or Kalmegh and is commonly known as ‘king of bitters’. It is extensively used as home remedy for various diseases in Indian traditional system as well as in tribal system in India for multiple clinical applications. AimIn our present work, extracts of these ayurvedic plants were tested for their anticlastogenic, antimutagenic and anticarcinogenic properties against Aflatoxin B1 induced toxicity. Materials and methodsWe used the in vitro method i.e. human lymphocytes culture and in vivo method in bone marrow cells of albino mice, while the parameters studied included chromosomal aberrations (CA), sister chromatid exchanges (SCEs) and cell growth kinetics (RI) both in the presence as well as in the absence of exogenous metabolic activation system for in vitro studies, whereas total aberrant cells and the frequencies of aberrations were used for in vivo methods. ResultsA. paniculata extracts significantly reduced chromosomal aberrations from 35.0%, 62.0% and 69.0% level [at 24, 48, and 72h due to Aflatoxin B1] to 21.72%, 44.0% and 52.0%, similarly sister chromatid exchanges were reduced from 14.60 per cell to 7.50 per cell at 48h of treatments and replication index was enhanced in vitro for each concentration and duration of treatment. ConclusionIn conclusion A. paniculata extracts significantly reduced the number of aberrant cells and frequencies of aberration per cell at each concentration and duration of exposure in vivo; similarly it reduced chromosomal aberrations and sister chromatid exchanges and replication index was enhanced in vitro that was statistically significant at <0.05 level.

The effect of complementary and alternative medicines on CYP3A4-mediated metabolism of three different substrates: 7-benzyloxy-4-trifluoromethyl-coumarin, midazolam and docetaxel

Concomitant use of complementary and alternative medicine (CAM) and anticancer drugs can affect the pharmacokinetics of anticancer drugs by inhibiting the metabolizing enzyme cytochrome P450 3A4 (CYP3A4) (EC 1.14.13.157). Several in vitro studies determined whether CAM can inhibit CYP3A4, but these studies revealed contradictory results. A plausible explanation for these conflicting results is the use only of a single model CYP3A4 substrate in each study. Therefore, the objective was to determine the potential of selected CAM (β-carotene, Echinacea, garlic, Ginkgo biloba, ginseng, grape seed extract, green tea extract, milk thistle, saw palmetto, valerian, vitamin B6, B12 and C) to inhibit CYP3A4-mediated metabolism of different substrates: 7-benzyloxy-4-trifluoromethyl-coumarin (BFC), midazolam and docetaxel. The effect of CAM on CYP3A4-mediated metabolism of an anticancer drug has never been determined before in vitro, which makes this study unique. The oncolytic CYP3A4 substrate docetaxel was used to establish the predictive value of the model substrates for pharmacokinetic interactions between CAM and anticancer drugs in vitro, and to more closely predict these interactions in vivo. The inhibition of CYP3A4-mediated metabolism of 7-benzyloxy-4-trifluoromethyl-coumarin (BFC) by CAM was assessed in Supersomes, using the fluorometric CYP3A4 inhibition assay. In human liver microsomes (HLM) the inhibition of CYP3A4-mediated metabolism of midazolam and docetaxel was determined, using liquid-chromatography coupled to tandem mass spectrometry (LC-MS/MS). The results confirmed grape seed and green tea as potent inhibitors and milk thistle as moderate inhibitor of CYP3A4-mediated metabolism of BFC, midazolam and docetaxel. Clinical studies are required to determine the clinical relevance of the determined CYP3A4 inhibition by grape seed, green tea and milk thistle.

Use of alcohol and drugs among health professionals in Norway: a study using data from questionnaires and samples of oral fluid

Working under the influence of drugs and/or alcohol may affect safety and job performance. However, the size of this possible problem among health professionals (HPs) is unknown. The aim of this study was threefold: (i) to analyze samples of oral fluid and self-reported data from questionnaires to investigate the prevalence of alcohol and drugs among a sample of HPs in Norway, (ii) to study self-reported absence from or impairment at work due to alcohol and/or drug use, and (iii) to examine whether such use and absence/impairment due to such use depend on socio-demographic variables.A total of 916 of the 933 invited HPs from hospitals and pharmacies participated in the study (participation rate = 98.2%), and 81.1% were women. Associations were analyzed in bi-variate cross tables with Chi-square statistics to assess statistical significance.Alcohol was not detected in any of the samples. Ethyl glucuronide, a specific alcohol metabolite, was found in 0.3% of the collected samples. Illicit drugs and medicinal drugs were identified in 0.6% and 7.3% of the samples, respectively. Both analytical results and self-reported use of alcohol and drugs during the past 12 months indicate that recent and past year alcohol and drug use was lower among HPs than among workers in other business areas in Norway, Europe and US. Nevertheless, several HPs reported absence from work due to alcohol (0.9%) and medicinal drug use (0.8%) during the past 12 months. A substantial part (16.7%) of the self-reported medicinal drug users reported absence from work because of use of medicinal drugs during the past 12 months, and more than 1/4 of those reported in-efficiency at work because of the use of medicinal drugs during the past 12 months. Reduced efficiency at work due to alcohol use during the past 12 months was reported by 12.2%.This sample of HPs seldom used illicit drugs, few had a high level of alcohol consumption, and few tested positive for medicinal drugs. Absence or hangover related to the use of medicinal drugs or alcohol appeared to be a bigger issue than the acute intoxication or the use of illicit drugs.

Recent Development of Benzotriazole-based Medicinal Drugs

The extensively clinical use of triazole-based medicinal drugs has been promoting increasing effort to develop new structural triazole derivatives. Benzotriazoles as fused aromatic nitrogen heterocycles of benzene ring with triazole exhibit wide potentialities in medicinal chemistry since some anticancer benzotriazole compounds like vorozole and 4,5,6,7-tetrabromo-1H-benzotriazole (TBB) were used in clinical therapy. The benzotriazole related investigations are becoming increasingly active. On the basis of authors’ researches and other literature in recent five years, this work for the first time gave a comprehensive review on the latest and outstanding developments of benzotriazole compounds in medicinal chemistry, including as anticancer, antifungal, antibacterial, antitubercular, antiviral, antioxidative, antiparasitic, antioxidative agents and so on. Hopefully, this contribution will be helpful to develop benzotriazole-based drugs with high bioactivity and low toxicity.