Resource use during systematic review production varies widely: a scoping review.

OBJECTIVE: We aimed to map the resource use during systematic review (SR) production and reasons why steps of the SR production are resource intensive to discover where the largest gain in improving efficiency might be possible. STUDY DESIGN AND SETTING: We conducted a scoping review. An information specialist searched multiple databases (e.g., Ovid MEDLINE, Scopus) and implemented citation-based and grey literature searching. We employed dual and independent screenings of records at the title/abstract and full-text levels and data extraction. RESULTS: We included 34 studies. Thirty-two reported on the resource use-mostly time; four described reasons why steps of the review process are resource intensive. Study selection, data extraction, and critical appraisal seem to be very resource intensive, while protocol development, literature search, or study retrieval take less time. Project management and administration required a large proportion of SR production time. Lack of experience, domain knowledge, use of collaborative and SR-tailored software, and good communication and management can be reasons why SR steps are resource intensive. CONCLUSION: Resource use during SR production varies widely. Areas with the largest resource use are administration and project management, study selection, data extraction, and critical appraisal of studies.

[Efficacy of Management for Rational Use of Antibiotics in Surgical Departments at a Multi-Disciplinary Hospital: Results of a 7-year Pharmacoepidemiological Research].

Background: Irrational medicine use including excessive use and abuse of antibiotics remains a crucial problem for the healthcare systems. In this regard, studies examining approaches to improving the clinical use of medicines are highly important. Aim: to assess the efficacy rate of management for the rational use of antibiotics in surgical departments of a multi-disciplinary hospital. Material and Methods: The intervention complex combined the research, educational, and methodological activities: local protocols for perioperative antibiotic prophylaxis (PABP) for various surgical departments were developed; local PABP protocols were discussed with the physicians of specialized surgical departments; official order on implementation of PABP was issued; the list of drug prescriptions for registration of the first pre-operative antibiotic dose was changed; audit and feedback processes were introduced as well as consultations of a clinical pharmacologist were implemented. We assessed the efficacy rate of the interventions basing on the changes in consumption of antibiotics (both quantitatively and qualitatively) at surgical departments of a hospital using ATC/DDD methodology. Comparison of the studied outcomes was performed before and after the intervention implementation and between the departments (vascular and abdominal surgery). The consumption of antibacterial agents (ATCJ01) was measured as a number of defined daily doses (DDD) per 100 bed-days (DDD/100 bed-days, indicator recommended by the World Health Organization, WHO) and DDD per 100 treated patients (DDD/100 treated patients). Results: From 2006 to 2012, a decrease in antibacterial consumption in surgical departments by 188 DDD/100 treated patients was observed. We obtained the opposite results when using an indicator of DDD/100 bed-days (increase by 2.5 DDD/100 bed-days) which could be explained by the dependence on indices of overall hospital work and its changes during the examined period. Observed changes in antibacterial consumption varied in different surgical departments. The most pronounced positive changes were noted in the department of vascular surgery: decrease in total antibacterial consumption by 298 DDD/100 treated patients, decrease in the use of cephalosporins of the III generation from 141 to 38 DDD/100 treated patients. These positive changes were accompanied by the same (low) level of consumption/use of reserve antibiotics. In the department of abdominal surgery, there was no decrease in total antibiotic consumption, as well as in consumption of broad-spectrum cephalosporins of the III generation and fluoroquinolones, and we observed an increase in the use of reserve antibiotics (carbapenems) during the study period. Positive changes in antibiotic consumption were associated with the positive attitude of the manager/head of the department towards interventions: we observed the most pronounced decrease in antibiotic consumption straight after the publication of the administrative order on perioperative antibacterial prophylaxis. Conclusion: The combination of scientific, educational, and methodological interventions is effective for improving antibiotic application. The study results provide the rationale for analyzing the drug consumption using the DDD/100 treated patients measure in addition to the WHO-recommended indicator of DDD/100 bed-days which depends on overall hospital performance.

[ANTIOXIDANT ACTIVITY OF XYMEDONE IN RATS WITH CHRONIC AUTOIMMUNE INFLAMMATION].

Effects of drug xymedone (in comparison to ionol) in a group of 32 white rats with experimental model of chronic autoimmune inflammation of rat paws (induced by Freund's adjuvant) were studied by measuring the volume of paw edema and determining the levels of lipid peroxidation (LPO) products and the activity of antioxidant enzymes in various tissues. Chronic autoimmune inflammation induced by Freund's adjuvant was characterized by the LPO intensification and disturbances of the level of antioxidant enzymes. Intragastric administration of xymedone (2,2-dihydro-4,6-dimethyl,-N-(ß-oxy-ethyl)-2-pyrimidon) at a dose of 169 mg/kg and reference drug ionol (2,6-ditretbutyl-4-methylphenol) at a dose of 220 mg/kg increased the activity of serum antioxidant enzymes by 19% and 11%, respectively, decreased the serum level of nitrite ion by 62% and 50%, and reduced the levels of LPO products in rat blood and homogenates of liver, kidney, and spleen by up to 80% (p < 0.05).

[NEW APPROACH TO COMPARING NSAID EFFICACY BY LONG-TERM MONITORING OF EXPERIMENTAL INFLAMMATION MODELS.]

Experiments on inflammatory edema modeling by sub-plantar injection of carrageenan lambda (1 %) and formalin (2 %) showed substantial differences betwe- en the two models during long-term observation, including irreversible damage caused by formalin (at reversible carrageenan action) and high intensity of for- malin edema (in contrast to carrageenan edema) in mice. We propose a new approach to evaluation of the so-called total inflammatory burden (experimental analog of disease outcome) by calculating the area under the inflammation intensity versus time curve. With the use of this approach, we showed the absence of any effect of conventional NSAIDs (naproxen, diclofenac. indomethacin) on the total inflammatory burden induced by carrageenan or formalin injections in mice and rat paw edema models. These results show the need for using new approaches in the search for potential anti-inflammatory agents.

POST-ANESTHETIC REHABILITATION PERIODS AND ANESTHESIA DOSAGE FOR LAPAROSCOPIC CHOLECYSTECTOMY: RELATIONSHIP TO THE TOTAL OXIDATIVE CAPACITY OF LIVER.

Analysis of the results of pharmacological phenotyping using antipyrine test prior to providing anesthesia for laparoscopic cholecystectomy showed that trimeperidine (promedol) dosing with allowance for the total oxidative capacity of liver and the patient mass allows the periods of post-anesthetic rehabilitation to be controlled. Clear algorithm of trimeperidine dosing based on established indices of the total oxidative capacity of liver and is yet nor developed because of restricted sampling set. The obtained results show expediency of using and studying antipyrine test as a simple, cheap, and informative method of individual anesthesia dosing for increasing the adequacy of general anesthesia.

Russian translations for Cochrane.

BACKGROUND: Cochrane collaboration has made a huge contribution to the development of evidence-based medicine; Cochrane work is the international gold standard of independent, credible and reliable high-quality information in medicine. Over the past 20 years the Cochrane Collaboration helped transforming decision-making in health and reforming it significantly, saving lives and contributing to longevity [1]. Until recently, Cochrane evidence were available only in English, which represents a significant barrier to their wider use in non-English speaking countries. To provide access to evidence, obtained from Cochrane Reviews, for health professionals and general public (from non-English-speaking countries), bypassing language barriers, Cochrane collaboration in 2014 initiated an international project of translating Plain language summaries of Cochrane Reviews into other languages [2, 3]. Russian translations of Plain language summaries were started in May 2014 by the team from Kazan Federal University (Department of Basic and Clinical Pharmacology; 2014-2015 as an Affiliated Centre in Tatarstan of the Nordic Cochrane Centre, since August 2015 as Cochrane Russia, a Russian branch of Cochrane Nordic, Head - Liliya Eugenevna Ziganshina) on a voluntary basis. OBJECTIVE: To assess the quality of Russian translations of Cochrane Plain Language Summaries (PLS) and their potential impact on the Russian speaking community through user feedback with the overarching aim of furthering the translations project. METHODS: We conducted the continuous online survey via Google Docs. We invited respondents through the electronic Russian language discussion forum on Essential Medicines (E-lek), links to survey on the Russian Cochrane.org website, invitations to Cochrane contributors registered in Archie from potential Russian-speaking countries. We set up the survey in Russian and English. The respondents were asked to respond to the questionnaire regarding the relevance and potential impact of the Cochrane Russian translations project, topics of interest in the field of health and health care, the quality and clarity of translated content, the preferred style of presentation and suggestions to improve the quality of translations of Plain language summaries of Cochrane Reviews. RESULTS: Currently the team of translators includes volunteers from the staff, Masters and PhD students of the Department of Basic and Clinical Pharmacology of the Kazan Federal University, and Kazan Medical University, our colleagues from Kazan and other cities of Russia, from the Republic of Armenia and the USA. By September 20th 2015, 446 Plain language summaries of Cochrane Reviews were translated into Russian and published on the web-site http://www.cochrane.org/ru/evidence. Our project "Russian translations for Cochrane" has already covered a wide range of health priority areas with translations of Plain language summaries and abstracts of the most topical and priority Cochrane reviews. During the period from 03.03.2015 to 20.09.2015 we received 113 answers from our respondents (103 answers in Russian and 10 answers in English). These were representatives of the medical and pharmaceutical professions (60%), representatives of non-medical professions (17%), students/graduate students (16%), retirees (4%) and others categories of citizens among the respondents. Half of the respondents (50%) belonged to the age group of 36-60 years, followed by the group of 18-35 years (41%). According to the survey the vast majority of respondents consider that the Cochrane Russian translations project is needed for Russia and Russian speaking countries (94%; n = 106), it is needed for their work, studies, and life in general (91%; n = 103). Nobody answered "No" to the question: "Do you think that this project is needed for Russia and Russian-speaking countries?" Information from the Cochrane evidence can affect (change) individual practice and/or attitude to drugs or diagnostic procedures of 87% (n = 98) of respondents. Only two people answered negatively to this question. However, only one third of respondents would like to become volunteer members of the translations project. The Russian texts of translations of Cochrane summaries and their main message were completely understandable or mostly clear to the vast majority of respondents (92%; n = 104). Respondents, proficient in English (n = 61), answered that the Russian-language translations fully complied (43%; n = 26) or in general corresponded to (57%; n = 35) the original English text. The majority of respondents (85%, n = 96) rated the quality of the translated texts as excellent and good. "More than half of respondents (61%; n = 69) would prefer the translations to be adapted to the usual style of presentation in Russian. The respondents agreed that mistakes, or typos or both very few. Our respondents provided valuable suggestions for further improvement of the Russian translations project. We would like to present here some of these: "More translations needed", "The ultimate goal... is to try to adapt the summaries to Russian language style as much as possible. This is a very challenging task, however and at present format the summaries are already great", "Go great as you do!" "Move forward and be efficient!" "Distribute information about the project through social networks and different means of social media", "Studying Cochrane Database should be included in the Russian medical school's curriculum at a much larger extent than it is included (if at all) now. It would be beneficial for high school students as well." CONCLUSIONS: The survey provided positive feedback on the Russian translations project concerning the clarity and quality of Russian texts and overall satisfaction of the readers. It confirmed the importance and relevance of the Russian translations project for Russian speaking audience, representing various professions and age groups. The survey results with detailed feedback contribute to further improvement of the Russian translations project. LIMITATIONS: Selective and subjective evaluation of translations by the respondents, difficulties with clear criteria for the objective evaluation. Further quality improvement of original PLS texts would contribute to higher translation quality. ACKNOWLEDGMENTS: We would like to thank Juliane Reed, Coordinator of the Cochrane Translations Project, Professor Peter C Gøtzsche, Director of the Cochrane Nordic, co-founder of the Cochrane Collaboration, Cochrane leadership and the global Cochrane network together with the leadership of the Kazan Federal University for continuous encouragement, spirit and support.

Towards the rational use of medicines.

BACKGROUND: Rational use of medicines remains to be one of the most challenging problems in health systems worldwide [1, 2]. ABC/VEN-analysis has been recommended for use by the World Health Organization (WHO) and has been used in health care practice globally since 1981. It represents the simple and effective method of analysis of medicine expenditures, identifying priority groups of medicines, the use of which, when improved, may provide the greatest clinical and economic impact. ABC analysis provides an accurate and objective picture of budget expenditures on medicines. VEN-analysis helps to prioritize between various medicines in their selection for procurement and use within a drug supply system [3-5]. OBJECTIVE: To assess the impact of introduction of evidence-based principles in the practice of medicine procurement and use on budget expenditures on medicines of a multidisciplinary health facility for the period of four years (2011-2014). METHODS: ABC/VEN analysis was carried out in a multidisciplinary health facility with over 1000 beds (an average number of beds for three years), which is responsible for provision of care to the population of about 1.4 million people. The analysis was carried out on the basis of information on medicine expenditures for 4 years: 2011 (1st year), 2012 (2nd year), 2013 (3rd year) and 2014 (4th year). When assigning VEN categories of medicines we used expert method: assignment of categories was carried out by clinical pharmacologists after reviewing all available evidence on effectiveness, safety and cost-effectiveness compared to other drugs in this group. In 2013, we implemented educational intervention, including detailed discussion of the results of the ABC/VEN-analysis for the years 2011-2012 from the standpoint of evidence-based pharmacology and recommendations for medicine procurement. In 2014, we delivered training workshop for the heads of clinical departments on evidence-based principles in clinical pharmacology and rational use of medicines. RESULTS: Medicines expenditures of the studied health facility for the year 2014 were less than for the year 2013, which was the important decrease reversing the trend of increasing medicines expenditures of the last three years: 2011 - 59,868,963 roubles; 2012 - 85,324,084 roubles, 2013 - 107 303 390 roubles, and 2014 - 74,416,692 roubles. The number of International Non-proprietary Names (INN) of medicines used in 2014 was 519, which was the highest number for the four years of the study: 2011 - 429 INN, 2012 - 432 INN, 2013 - 513 INN, and 2014 - 519 INN. Nearly 40% of the funds spent in 2014 on medicines have been used for Vital medicines: 2011 - 26%, 2012 - 39%, 2013 - 25%. Expenditures on Non-essential medicines in 2014 were about the same as in previous years - 14% of total medicine expenditures: 2011 - 16%, 2012 - 13%, 2013 - 15%. However in absolute numbers (roubles) expenditures on non-essential medicines decreased compared to the years 2013 and 2012: 2011 - 9,428,135 roubles, 2012 - 11,129,388 roubles, 2013 - 15,578,325 roubles, 2014 - 10,616,023 roubles.Expenditures on solutions for infusion (sodium chloride, Ringer's solution, dextran, glucose, hydroxyethyl starch) decreased as compared to the year 2013, but still remained high, thus indicating on the abuse of parenteral methods of drug administration. The portion of expenditures on isotonic sodium chloride solution and hydroxyethyl starch in 2014 decreased compared to the year 2013. We found a positive trend in the structure of expenditures on antibacterial agents: in 2014 expenditures on fluoroquinolones decreased nearly fivefold compared to 2013, expenditures on cephalosporins also decreased, but not so dramatically. However, there was a significant increase in expenditures on carbapenems, more than twofold compared with the year 2013. In 2014 we noted a twofold decrease in expenditures on medicines affecting blood, including antithrombotic agents, hemostatics and antianemic medicines, as compared to the values of the year 2013. In 2014 there was also a decrease in expenditures of cardio-vascular medicines, medicines affecting nervous system, alimentary tract and metabolism. CONCLUSIONS: Introduction of evidence-based principles through educational interventions at a multidisciplinary health facility resulted in a number of changes towards more rational medicine use. Regular educational interventions for practicing physicians and heads of clinical departments of health facilities that promote rational prescribing are needed.

Anti-inflammatory and anti-oxidant properties: Is there a link?

BACKGROUND: It is believed that the anti-inflammatory activity of medicines is closely related to their antioxidant activity. However, in clinical practice rigorous evidence-based medicine approach fails to reveal important effects of antioxidants on patient important outcomes in inflammatory disorders, as has been shown by a number of Cochrane reviews [1-3]. OBJECTIVE: To evaluate anti-inflammatory and antioxidant effects of newly developed pharmacological agents: dimephosphone and its structural analogues ephorane and mephoprane, and xymedon, in comparison with prednisolone and etidronate in experimental animal model of adjuvant arthritis. METHODS: Experiments were conducted in 64 white mongrel rats of both sexes weighing 180-200 g, which were divided into 8 groups 8 rats each (4 males and 4 females each), kept under standard vivarium conditions with certified feeding ration (kombikorm). The study was approved by the local ethics committee. We induced adjuvant arthritis by administration under the plantar aponeurosis of the left hind paw of 0.1 ml of Freund's adjuvant (Sigma) in rats of 7 study groups. The groups were as follows: 1st group - intact animals (control); 2nd group - animals to whom the solvent (distilled water) was administered with intra-gastric tube in corresponding volume (control of the model); 3rd - 8th study groups, in which animals were administered with study agents each at a dose of 1 mmol/kg body weight: dimephosphone, ephorane, mephoprane, xymedon, etindronate and prednisolone. The intensity of the modeled arthritis was determined by measurements of paw volumes with plethysmometer (UgoBasile). We calculated the difference in rat paw volume before the administration (baseline) and after administration of Freund's adjuvant at 3, 7, 11, 15, 20, 27, 31, 38, 41 days. The development of secondary arthritis was documented by the increase in volume of both hind and fore paws and tails. On the 41st day of the experiment the animals were sacrificed under light ether anesthesia and exsanguinated. The blood was used to determine the activity of catalase and peroxidase, the content of the total, reduced and oxidized glutathione, the level of ceruloplasmin, conjugated dienes of unsaturated fatty acids (DC), TBA-interacting products (MDA), and the total antioxidant activity of serum (AOA). The results were processed statistically using the Student's t-test. RESULTS: The primary reaction to the Freund's adjuvant in a form of swelling of the ankle joint of the left hind paw was observed at 24 hours after its injection. External clinical manifestations of the modeled disease were more pronounced on the third day: local inflammatory reaction (redness, swelling, ulceration) was seen in all the animals at the injection site with the increase of the paw volume. On the 11th day of the experiment 20% of the animals developed secondary arthritis. The study agents dimephosphone, ephorane, and prednisone exerted anti-inflammatory effect decreasing the volume of left hind paws by 45%, 46% и 27% respectively on the 40th day of experiment. Mephoprane did not affect the primary inflammatory response to the Freund's adjuvant (rats' left hind paws), however it reduced the volume of the contralateral right paw (secondary arthritis) by 90% on the 20th day of the experiement. This ant-inflammatory effect was accompanied by documented antioxidant activity in case of dimephosphone, ephorane, prednisolone, but not mephoprane. Dimephosphone reduced the levels of lipid peroxidation products in rats blood by 46% (DC) and by 25% (MDA). Ephorane also reduced the levels of lipid peroxidation products in the blood by 46% (DC) and by 25% (MDA), increasing the level of glutathione by nearly half, both the total and the reduced form. Prednisolone reduced the level of lipid peroxidation products in blood by 61% (DC), but not the TBA-interacting products. Mefopran did not affect the blood level of lipid peroxidation products. Xymedon and etidronate showed no anti-inflammatory effect. Xymedon demonstrated anti-oxidant properties, decreasing the blood levels of lipid peroxidation products, while etidronate seemed to behave in pro-oxidant mode, increasing the blood levels of lipid peroxidation products. CONCLUSIONS: The effects of studied agents on the intensity of inflammation and lipid peroxidation were inconsistent. The results of the study did not show a clear link between anti-inflammatory and anti-oxidant activity. Further research in potential anti-inflammatory activity of new drugs exhibiting antioxidant properties needs to be done before recommending their use in clinical practice.

Clinical conferences for physicians: Who sets the agenda?

BACKGROUND: Clinical conferences are generally defined as scheduled events at which practicing physicians themselves present to their colleagues interesting clinical cases, share their new experiences and learn about the latest achievements of medical science and practice. The value of a clinical conference is thought to be in direct communication between physicians, in analysis of topical issues in a given specialty with the aim to improve the quality of care. Speakers based on their own observations and studies reveal the most urgent problems, analyze results and offer potential decisions to their colleagues interested in the same questions. The event format may be different: workshops, highly specialized sections, round tables and seminars with participation of the leading specialists in a given field. These conferences are generally organised by the Ministries and Departments of Health, by leading research and/or educational institutions in the field, by recognised medical centres and other institutions. Recently pharmaceutical companies got actively involved in medical events, acting as sponsors of various scientific conferences and congresses, however threatening the mission of these events [1]. This brings up some uneasy questions: who are the medical conferences for? Who is in charge of setting the conference agenda? Do they contribute to evidence-based medicine; do they contribute to better health? Unfortunately, there is a trend to duplication or multiplication of conferences: various agencies and departments deliver the same conferences, presentations at which are often pre-arranged by pharmaceutical companies and do not have clear scientific novelty, while the conferences themselves have largely transformed into advertising of new pharmaceuticals or new technologies [2]. Pharmaceutical corporations sponsor invited speakers paying for their trips and paying honoraria, organising cocktail parties as part of medical activities. With the help of leading experts with impressive titles serving as speakers at the conferences, pharmaceutical companies are trying to be as close as possible to routine practice of prescribing of certain drugs, manipulating evidence, controlling scientific societies as well as the process of clinical guideline development and publication of research results [3]. The degree of expert involvement depends on their level of influence [4]. OBJECTIVE: We aimed to study how often regular medical practitioners attend these conferences; to analyse who were keynote speakers and where they were coming from; to identify which organizations were responsible for organisation of these conferences and for sending out invitations to these conferences and for disseminating information about them. METHODS: We summarized all the invitations (printed on paper) received by one regular medical practitioner employed with the outpatient clinical of the city of Kazan for the period of two years (2012-2013). RESULTS: During the study period (2012-2013), a regular medical practitioner received 47 printed paper invitations to scientific conferences: 22 in 2012 and 25 in 2013. The conferences were not distributed evenly over the months of the years. November appeared to be the month with the highest density/number of medical conferences: 7 conferences in 2012 and 10 in 2013. If the distribution was even, then we could calculate the number per month dividing the number per year by 9 active months (excluding July, August and September). This resulted in 2.4 and 2.8 conferences per month. Among these studied conferences 4 were organized by public health agencies: invitation tickets were accompanied by the corresponding official order to organise a conference, issued by the Health Department. Noteworthy, that 2 of these conferences were held in conference rooms of the largest hotels of the city. Forty-one out of 47 medical conferences were sponsored by big pharma: either jointly with the major medical higher educational institutions of the city or plainly by pharmaceutical companies. Seventeen conferences were held during official working hours, in the first half of the day. Not only the logo of the pharmaceutical companies was printed on invitation tickets, but there was also an advert of the promoted pharmaceutical brand.Nine conference invitations contained invitation to dinner. In one of the invitations to a conference on neuroscience it was written: "dinner under the unforgettable music". Two conference invitations contained invitation to a lunch. Programs of 20 conferences (which were included) listed guest lecturers, coming from the leading medical universities in Moscow and St. Petersburg. Opinion leaders' involvement: some of the leading experts acted as speakers from 4 to 7 conferences a month in this sample conference invitations package of a regular polyclinic physician. CONCLUSIONS: In 2012-2013 health practitioners were invited to attend medical conferences regularly, at least 2 times a month, with November being the busiest month. The keynote speakers were the opinion leaders from the local medical educational institutions and visitors from Moscow and St. Petersburg; their involvement with the conferences was repetitive. Governmental institutions jointly with big pharma were responsible for organisation of these conferences and attracting audience.Limitations of these observations:Unfortunately, the information on printed-paper conference invitations was not complete because not all tickets have survived. From the interview with the physician we know that in addition to these printed on paper invitations there were many invitations and alerts sent out by e-mail, SMS messages and personal phone calls, making the regularity of these conferences much higher. The physician, who kindly provided this information to us, asked not to be named or thanked in any public presentation of the results of these analyses.

[MODELING INFLAMMATORY EDEMA: ARE THE MODELS INTERCHANGEABLE].

Experimental modeling of inflammatory edema by sub-plantar injection of carrageenan and formalin in mice and rats is widely used to evaluate potential anti-inflammatory activity of new drugs. This systematic analysis of published data showed that carrageenan induced paw edema model is used for evaluating the anti-inflammatory activity mostly in rats rather than mice. Formalin induced paw edema in rats and mice is used primarily for evaluation of the analgesic activity of drugs. Taken together, the results of this systematic review of available literature on edema modeling substantiate recommendation to use carrageenan paw edema in rats and formalin paw edema in mice as complementary, but not interchangeable models of inflammation.

[Experimental comparative study of the analgesic activity of the diurnal anxiolytic mebicar, amitriptyline, and diazepam].

It is established that mebicar, amitriptyline, and diazepam administered intraperitoneally at therapeutic doses increase the pain thresholds in mice as manifested in "hot plate" analgesia test. Mebicar was more effective than diazepam and not inferior to amitriptyline in increasing the pain thresholds at earlier time points.

[Phenotyping by total oxidative hepatic capacity in patients undergoing laparoscopic cholecystectomy: two categories of patients and duration of post-anesthesia rehabilitation].

In patients, undergoing laparoscopy cholecystectomy, two phenotype categories were identified on the basis of the total oxidative hepatic capacity determined by antipyrine test, which differed by duration of post-anesthesia rehabilitation. The potential of antipyrine phenotyping for individualisation of anesthetics' dosing is discussed.

[Anti-inflammatory properties of antidepressants (a review of experimental results)].

The review presents comparative description of anti-inflammatory effects of antidepressants from various classes studied on carrageenan- and formalin-induced paw edema in rats. The role of the central and peripheral components in the mechanisms of anti-inflammatory activity and the drug effects on production of mediators and modulators of inflammation is discussed.

[Dimephosphone shows anti-inflammatory and anti-oxidative activity on chronic autoimmune inflammation model].

The anti-inflammatory activity of dimephosphone, xydiphone (ethidronate), and ionol (dibunol) and their effects on lipid peroxidation (LPO) indices and the activity of antioxidant enzymes in blood were studied on the model of Freund adjuvant induced arthritis in white laboratory rats. The Freund adjuvant induced chronic arthritis and increased the concentrations of PLO products and nitrite ions in the blood plasma. Only dimephosphone showed an anti-inflammatory action. Dimephosphone and ionol inhibited the LPO, whereas xydiphone did not influence the LPO indices in the blood.

[Anti-inflammatory effects of amitriptyline, diazepam and mebicar using model of acute carrageenan-induced paw edema in rats].

The anti-inflammatory activity of amitriptyline, diazepam and a new, Russian tranquilizer mebicar was studied in a wide range of therapeutic doses on carrageenan-induced paw edema in rats. Mebicar at low doses showed greater and longer (up to 24 h) lasting anti-inflammatory activity as compared to that of amitriptyline and diazepam.

New specific marker of cytochrome P450 1A2 activity.

Various methods were proposed for phenotyping of patients by activity of cytochrome P450 1A2, each has some advantages and disadvantages. However, no reference parameters were developed for measuring CYP1A2 activity that could be used as a unified standard for phenotyping of patients. We propose a mathematic model of caffeine metabolism allowing calculation of rate constants for the formation of its primary metabolites. First-order rate constant of paraxanthine formation was tested as a new specific marker of isoenzyme 1A2 in healthy volunteers.

[Comparative analysis of dimephosphon, ionol, and xydiphone effects on indomethacin-induced gastric lesions in rats].

Gastroprotective activity of dimephosphon, xydiphone, and ionol and their effects on the lipid peroxidation (LPO) indices and the activity of antioxidant enzymes in blood and organ tissues were studied on the model of indomethacin-induced gastric lesions in white rats. The indomethacin-induced gastropathy leads to increased concentration of LPO products in blood plasma and tissues. Dimephosphon and ionol reduced the number of gastric lesions and prevented LPO activation. In contrast, xydiphone administration had no effect on indometacin-induced gastric lesions and was accompanied by increased concentration of LPO products in the blood, liver, kidneys, spleen and stomachs of rats.

[On the possibility of patient phenotyping on the basis of cytochrome p-450 1A2 isoenzyme activity using caffeine as the test substrate].

Reactions of caffeine biotransformation and enzymes participating in the caffeine metabolism via the paraxanthine pathway are reviewed. Data on the drugs metabolized mainly in cytochrome P-450 1A2 isoenzyme (CYP 1A2) are analyzed. Information on the phenotypes of CYP 1A2 activity in smoking healthy volunteers, women using oral contraceptives, diabetes patients, those with liver disorders, etc. is summarized. Methodological approaches to patient phenotyping with respect to CYP 1A2 activity as proposed in the available literature are analyzed.

[Chromatographic determination of caffeine and its metabolites in saliva and plasma].

The authors made a comparative analysis of the well-known high performance liquid chromatographic (HPLC) techniques to detect caffeine and its primary metabolites in saliva and plasma when during their oral administration. The studies yielded a new specific and sensitive procedure for HPLC analysis of caffeine and its major metabolites, whose distinctive feature was to simultaneously separate six substances with a possibility of determining the activity of the cytochrome P-450 isozymes 1A2, 2E1, and 3A4.