Press releases «Sanofi-Aventis».
After the first year of treatment, patients treated with Acomplia (Rimonabant) 5 or 20 mg, re-randomized to treatment with Acomplia (Rimonabant) in the same dose or placebo, using randomization ratio of 1:1 for 52 weeks (placebo group continued receiving placebo).

The results

The data presented indicate that treatment with Acomplia (Rimonabant) 20 mg for two years provided a significant decrease in body weight, amount of abdominal fat and severity of cardiovascular risk factors and metabolic disorders. Within two years, waist circumference, which is a simple measure of abdominal fat in patients in this group decreased by 8 cm (3,1 inches) versus 4.9 cm (1.9 inches) in the treatment with Acomplia (Rimonabant) 5 mg and 3.8 cm (1 , 5 inches) in the placebo group (p <0.001), 62.5% of patients lost more than 5% of initial body weight compared with 36.7% of patients in the group treated with Acomplia (Rimonabant) (5 mg) and 33.2% in the placebo group (p <0,001). During the same period, 32.8% of patients in group therapy with Acomplia (Rimonabant) (20 mg) lost more than 10% of body weight, compared with 20% in the group of Acomplia (Rimonabant) (5 mg) and 16.4% of patients in the placebo group (p <0.001).

Metabolic parameters also significantly improved in patients treated with Acomplia (Rimonabant) 20 mg for two years. Content of high-density lipoprotein cholesterol increased by 24,5% in group treatment with Acomplia (Rimonabant) 20 mg against 15,6% and 13,8% respectively in group treatment with Acomplia (Rimonabant) 5 mg and placebo (p <0,001). The content of triglycerides decreased by 9.9% in patients treated with Acomplia (Rimonabant) 20 mg for two years against 5,5% and 1,6% respectively in groups of Acomplia (Rimonabant) 5 mg and placebo (p <0,05).

Although patients with diabetes in the study did not include, the treatment with Acomplia (Rimonabant) 20 mg significantly improved insulin sensitivity compared with patients who received Acomplia (Rimonabant) 5 mg and placebo.

Effect of treatment with Acomplia (Rimonabant) for the maintenance of high-density lipoprotein cholesterol, triglycerides, fasting insulin and insulin sensitivity (as measured by Noma) was 2-fold more pronounced than expected, based on the achieved lower body weight (all figures p <0.05).

Particularly noteworthy is that the number of patients who were diagnosed with metabolic syndrome at baseline and treatment with Acomplia (Rimonabant) 20 mg for two years of research, has declined by about one third (p <0.001).

The safety profile and tolerability

For Acomplia (Rimonabant) 20 mg established safety and good tolerability compared with placebo, side effects were mostly mild and passes quickly. The overall incidence of treatment discontinuation due to adverse events during the first year amounted to 7,2%, 9,4% and 12,8% for placebo, Acomplia (Rimonabant) 5 mg and 20 mg of Acomplia (Rimonabant), respectively, the frequency of treatment discontinuation in patients who were randomized to continue treatment during the second year, amounted to 6,7%, 8,3% and 6,0% respectively, a new relationship of groups. In all groups, no differences were found in the indicators measured by the scale of the hospital anxiety and depression. In this study, and the two preceding shows that Acomplia (Rimonabant) had no significant effect on the ECG or heart rate.

Acomplia (Rimonabant) and the EU system

The EU system (endocannabinoid system) – a newly discovered physiological system in the body, which, according to experts, played a key role in the central and peripheral regulation of energy balance, metabolism of glucose and lipids, as well as control of tobacco dependence.

CB1 receptors are found in the brain, as well as in peripheral tissues such as adipocytes, which are associated with the metabolism of lipids and glucose. Consumption of excessive amounts of food, or chronic use of tobacco leads to hyperreactivity of the EU, that can run the mechanism of increasing food intake and fat accumulation, or, in the case of smoking, sustained tobacco dependence.

Acomplia (Rimonabant) – first of a new class of drugs – blockers of the first type of cannabinoid receptor (CB1). By selective binding of the central and peripheral CB1 receptors, Acomplia (Rimonabant) modulates the overactive EC system. The study results were obtained on reducing the severity of risk factors for cardiovascular disease by reducing the amount of abdominal fat and a corresponding improvement of metabolic parameters that go beyond the expected, based on the reduction of body weight.

New clinical research results RIO-North America suggest that Acomplia (Rimonabant) may become an important element in the arsenal of means of correction of cardiovascular risk factors.

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Advantages of Acomplia (Rimonabant) confirmed in the two-year study
Press releases «Sanofi-Aventis».

Results of two Phase III clinical trial in 3040 patients primeneiya Acomplia (Rimonabant) (Akomplia), the first representative of a new class of therapeutics – selective cannabinoid receptor CB1 blockers, indicate that the benefits achieved by the application of Acomplia (Rimonabant) 20 mg at the end of the first year of study, and persisted during the second years of therapy with good safety and tolerability compared with placebo. The results were submitted to the scientific community on scientific sessions of the American Heart Association in New Orleans (Louisiana), Dr. Xavier Pi-Sunyer, head of the Department of Endocrinology Hospital Center at Columbia University (New York), and principal investigator of the study.

Patients treated with Acomplia (Rimonabant) 20 mg for two years, decreased body weight and waist circumference, indicating a significant decrease in the number of abdominal fat – a key marker of cardiovascular disease. Patients were also achieved a significant increase in cholesterol high density lipoprotein, triglyceride reduction and improved insulin sensitivity.

Study RIO-North America – the largest of the studies of Acomplia (Rimonabant). His results are consistent with those of two previous large-scale studies on Acomplia (Rimonabant) – RIO-Lipids and RIO-Europe – and increase the volume of evidence demonstrating the efficacy and tolerability profile of the drug. Acomplia (Rimonabant) is designed for correction of cardiovascular risk factors, it provides a reduction of abdominal obesity, improving lipid and glucose metabolism, and promotes smoking cessation.

Obesity – the largest public health problem and one of the most frequent causes of death worldwide, mainly due to cardiovascular diseases. Obesity is usually defined by body mass index (BMI), but recent studies have shown that visceral (abdominal) obesity (the degree of its directly correlates with the size of waist circumference) is the best factor for predicting the risk of acute coronary syndrome than body weight or BMI [1 ]. 44% of U.S. adults waist circumference greater than the risk level (40 inches for men and 35 inches for women) [2]. Visceral type of obesity is associated with the causes of metabolic risk factors such as dyslipidemia or insulin resistance, which can lead to diabetes, myocardial infarction, stroke and other cardiovascular diseases. The decrease in visceral obesity is a recognized priority for preventing cardiovascular disease [3].

«Cardiovascular risk factors associated with obesity become more pronounced. Excessive amounts of abdominal fat is increasingly recognized as one of the most informative precursors of future cardiovascular events, – said Professor Pi-Sunyer. – Results of two studies RIO-North America confirm that Acomplia (Rimonabant) is an innovative and promising tool for long-term correction of obesity and associated cardiovascular risk factors in patients with abdominal obesity ».

Objectives and study design

The international, multicenter, randomized, double-blind, placebo-controlled trial of RIO-North America of the third phase, which compared the two methods of appointment to a fixed dose of Acomplia (Rimonabant) (5 and 20 mg once daily) compared with placebo during the same period – two years. The study involved 3040 patients from 72 centers in the U.S. and Canada.

Objectives of the study was to evaluate the effect of Acomplia (Rimonabant) on weight loss over one year and determine the ability of Acomplia (Rimonabant) to prevent weight gain is new in the second year of treatment, improvement of risk factors associated with abdominal obesity (measured by waist circumference) such as dyslipidemia , glucose metabolism and the metabolic syndrome, safety and tolerability of Acomplia (Rimonabant) in over two years.

After a week of screening patients received mild hypocaloric diet (by reducing daily caloric intake by 600 kcal compared to the energy needs of patients) and started to blind placebo once daily for 4 weeks. Thereafter patients were randomized to one of three treatment groups (placebo, Acomplia (Rimonabant) 5 mg and Acomplia (Rimonabant) 20 mg) for 52 weeks double-blind method with a ratio of 1:2:2 randomization.

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Rimonabant – first of a new class of medicinal drugs, whose action is based blocking that part of the brain that regulates food intake and activity of refining sugar and blood fats. It is approved in 37 countries, 18 of them, he goes under the name Acomplia ®. The first warnings about possible psychiatric effects of combining antidepressants and diet pills appeared in the summer of 2006. It took a year of research to determine the heavy side effects of the drug.

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On non-steroidal anti-inflammatory drugs
Non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely-appointed group of medicines worldwide. Every day, more than 30 million people in the world are taking any NSAIDs, 40% of them – aged 60 years.

The prescriptive list of basic (essential) Medicines (Essential Drug List. WHO, 1999) includes only a few funds belonging to a class of non-opioid analgesics, including two NSAIDs.

The selection of these funds to the list of essential medicines is due not only to their high therapeutic activity, but, most importantly, secure, proven long-term experience of many doctors around the world. Meanwhile, WHO experts stressed that the list is not a «frozen» document, it must be regularly reviewed and adapted to the conditions of individual countries should take into account the qualifications and experience of physicians, as well as new research.

As you know, the whole class of non-opioid analgesics can be divided into two large groups – nekislotnye acid and derivatives. And if the second, more narrowly, includes tools such as acetaminophen (paracetamol), metamizole (analgin) *, with only antipireticheskoy and analgesic activity, the first – all the so-called non-steroidal anti-inflammatory drugs, possessing a full spectrum of pharmacological activity – analgesic and anti-inflammatory antipireticheskim action.

The whole group of NSAIDs is also conventionally divided into a number of key «families» (subclasses) in accordance with the active substance, which they are derived.

Experts from different countries are united in the opinion that the differences in the effectiveness of NSAIDs are relatively small (Fries JF, Williams CA, Bloch DA, 1991). Reviews of several dozen clinical trials of various NSAIDs in osteoarthritis and rheumatoid arthritis did not give grounds to rank the drugs according to their effectiveness (Fries J., 1996). Although the number of NSAIDs is increasing, none of the new drugs can not be conclusively found to be more effective than aspirin or ibuprofen. The frequency of side effects arising from the admission of these drugs, also about the same, perhaps, the exception is ibuprofen in low doses (Brooks PM, 1988). At the same time, the systematization of data from randomized trials (McQuay H., Moore A., 1998), using the criterion of maximum total pain relief, which to some extent can objectify the potential relevance of various analgesics in anesthesia, gives rise to a definite hierarchy in analgetic activity many medicines.

If the effectiveness of drugs roughly equivalent, then the reason for their choice could be the relative safety. However, with few exceptions, there is little choice. NSAIDs is one of the most common causes of adverse reactions to drug treatment. In the UK, NSAIDs account for 5% of all prescribers, but they accounted for 25% of all adverse events reported to the Committee on Safety of medicines. According to official estimates, in the UK 3-4 thousand deaths annually due to side effects of NSAIDs. In the United States each year use of NSAIDs leads to more than 70 thousand hospitalizations and 7 thousand deaths.

For NSAIDs typical four main types of side effects: gastrointestinal reactions, including stomach ulcers, hypersensitivity, renal insufficiency after prolonged use, central nervous system dysfunction, including forgetfulness, inability to concentrate, insomnia, paranoia and depression. Less commonly observed liver damage, sometimes severe.

Data on the frequency of nephrotoxic adverse reactions during treatment with NSAIDs (Current Problems in Pharmacovigilance, 1994)

The number of message here, attributable to 100,000 prescriptions per year

All medicines in varying degrees, can be associated with undesirable side reactions. NSAIDs as a class of drugs characterized by a number of adverse reactions, and the difference in their severity is extremely small. In addition, these problems are potentially important for all patients without exception, regardless of the duration of therapy and age.

Gastrointestinal reactions as a manifestation of adverse reactions to NSAIDs are the most frequent and common to this class of therapeutic drugs. Clinically, these manifestations occur most difficult and are a major risk factor for death.

NSAIDs toxic effects on two independent mechanisms – local (a narrow) and the total generalized (systemic) effect.

One of the most reasonable points of view on the pathogenesis of NSAID-induced lesions of gastrointestinal system is that these specific complications of therapy due to non-selective suppression of synthesis of prostaglandins **.

Approximately 50% of patients with NSAID-gastropathy (yazvennno-erosive lesions of mucous membrane of the stomach and duodenal ulcers, bleeding), the disease can occur with virtually no symptoms, and thus detected very late. Such vital hazardous conditions may be the first and only sign of pathological changes in the gastrointestinal tract (this feature of NSAID-gastropathy is particularly pronounced in older patients). Moreover, quite often non-steroidal anti-inflammatory agents due to the peculiarities antiprostaglandinovoy activity can «obscure» symptoms of pathology of the gastrointestinal tract, thus impeding the diagnosis and treatment of disease. At the same time, a certain part of patients (30%) gastropathy is the only symptom of abdominal pain without pathological somatic changes. Between plagues, formed as a result of taking NSAIDs, and have arisen spontaneously, at random (ulcer), there is some difference. First, ulcers, resulting from NSAIDs, most often asymptomatic. Secondly, the gastric mucosa «adapted» to long-term effects of NSAIDs, so that 2-8 weeks after taking the drug reduced the acute lesion, and a number of experiments showed that the most dangerous may be considered the first months of receiving those funds.

It is believed that the risk of gastrointestinal bleeding is high as a target short-term, and during chronic administration of NSAIDs. At the same time, there is every reason to believe that it is the duration of admission to the greatest extent due to the major threat, even OTC NSAIDs. Long-term retrospective study (Kurata JH, Abbey DE, 1984), conducted in 4524 patients found that daily use of aspirin at a dose of 1000 mg (DCI – 6000 mg) for the prevention of myocardial infarction at 4 years increases the risk of ulcerative lesions in 10.7 times compared with the control group (not taking aspirin). One must bear in mind that the minimum doses of salicylates can be quite dangerous. Research (Naschitz J., 1989) have demonstrated that even a minimum dose of aspirin as 75-250 mg, may be the main cause of bleeding in the upper gastrointestinal tract in 8.2% of patients. At the same time one of the prospective studies (Lanza F., 1984) showed that a three-day short-term regular use of the safest of the NSAIDs, the drug – ibuprofen – a daily dose of 1600 mg (DCI – 2400 mg) can not cause morphologically significant changes in gastric mucosa.

Hypersensitivity reactions. One of the most important criteria for the use of NSAIDs as an analgesic for acute pain (traumatic or surgical origin) is an allergic-immunological status of the patient, the risk of bronchospasm (Szczeklik A., 1992). Acute asthma attacks aspirinzavisimoy develops in about 8-20% of adult asthmatics. In some patients it may be the first symptom of incipient asthma disease. The observed cross-correlation between asthma and bronchospasm aspirinzavisimoy applies not only to salicylates, but almost all NSAIDs. And considering the issue more broadly, it should be recognized that the appointment of acid derivatives of NSAIDs is contraindicated in patients with a history of any manifestation of the so-called «aspirin triad» – asthma, nasal polyposis, in ducts or intolerance to aspirin (Power I., 1993).

Data on the frequency of hepatotoxic adverse reactions during treatment with NSAIDs (Current Problems in Pharmacovigilance, 1994)

The number of message here, attributable to 100,000 prescriptions per year

Renal. It is believed that the adverse reaction from the kidney may be due to systemic non-selective suppression of prostaglandin synthesis, affecting the regulation of glomerular filtration, maintenance of fluid and electrolyte balance. These reactions usually occur in patients with a history of any kidney disease. In such cases, the main symptoms of adverse reactions may be acute renal failure, fluid retention, hyperkalemia.

Furthermore, we must take into account the possibility of cross-reactivity with the appointment of NSAIDs while taking diuretic drugs, especially in elderly patients. Most NSAIDs inhibit the action and increase the nephrotoxicity «loop» diuretics reduce the hypotensive effect benzotiazidov (Johnson AG, Seideman P., Day RD, 1993), which also greatly increases the risk of adverse reactions.

Abnormal liver function. Risk of drug hepatitis while taking NSAIDs is relatively small. We describe the exclusive cases of acute hepatotoxic reactions to the development of fatal outcome (Masana P. et al., 1986). All of them are associated with significant overdose and prolonged treatment. At the same time, in 1-4% of cases there may be asymptomatic moderate increase in the level of liver enzymes (Nasonov EL, Lebedeva OV, 1991).

Violation of the central nervous system. Reactions of neurotoxicity, manifested by headaches, some disorientation, confusion may occur while taking all NSAIDs, but most often they occur, when it comes to drugs, it is easy minuyuschih blood-brain barrier (Goodwin JS, Regan. M., 1982). All these reactions are most pronounced in older patients due to their age and physiological characteristics. In addition, this category of patients in connection with violation of attention and memory are at risk for accidental overdose (the so-called «aspirin intoxication»), which is easy to ignore.

Generalized data on the safety key NSAIDs. Since prior to 1997 studies on the tolerability of aspirin, ibuprofen and acetaminophen (the most widely used in everyday practice for treatment of low / moderate acute pain in adults) has been conducted, this problem is regarded as sufficiently relevant to public health. Accordingly, in 1997-1999, was followed by a global, randomized, multicenter study focused on obtaining reliable data for objective comparison of tolerability of aspirin, ibuprofen and paracetamol in standard recommended doses and intermittent on the acute pain of various etiologies (The PAIN Study: Paracetamol, Aspirin and Ibuprofen New Tolerability Study / / Clin. Drug. Invest, 1999, vol. 18, № 2, pp. 88-98; Moore N., Van Ganse E., et al. A comparison of the tolerability of Ibuprofen, Acetominophen and Aspirin for short-term analgesia / / Proceedings of the 9th World Congress on Pain / Eds. M. Devor, MC Rowbotham, Z. Wiesenfeld-Hallin. Seatle: IASP Press, 2000, p. 809-817).

The results showed that all the main characteristics of tolerability of ibuprofen equivalent indicators tolerability of paracetamol and aspirin higher than portability. In this regard, you may need to reconsider the priorities concerning the use of first-line analgesics for short-term treatment of conditions involving pain syndrome in general practice. First recommended to prescribe ibuprofen because of poorer tolerability of aspirin and the potential dangers of paracetamol overdose.

And finally, what it is worth noting: most of the newer drugs cost much more than appeared long ago. Thus, it is known that the use of a simple reproduction of analgesic such as ibuprofen, costing 2-8 times cheaper than the use of a new, «modern» NSAIDs. If appointed NSAIDs with misoprostol to reduce the risk of ulcerative lesions of the stomach and intestines, then the cost of treatment is even higher. This proves once again that the use of long-known NSAIDs, such as aspirin and ibuprofen, is much more profitable.

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The most important properties of some strains of germs are their antagonistic activity of many pathogenic and conditionally pathogenic microorganisms, high enzymatic activity, allowing substantially regulate and stimulate digestion; protivoallergennoe and antitoxic action and several others.

That such properties has drug Biosporin, which (perhaps the only one of probiotics on the basis of bacilli) includes not one but two strains – B.subtilis and B. licheniformis. They complement each other on the spectrum of antagonistic activity, production of enzymes and amino acids and, very importantly, do not suppress with the resident microorganisms. Bacillus (antagonistic activity of strain B. subtilis), included in Biosporin actively inhibit pathogenic microorganisms.

The unique ability of the drug is suppression of Candida, Staphylococcus, Campylobacter, Yersinia, including the antibiotic. This antagonistic activity Biosporin significantly higher in comparison with baktisubtilom, tsereobiogenom and enterogerminom.

Biosporin widely used for the correction of violations of the microflora (dysbacterioses), caused by irrational use of antibiotics, malnutrition, past infectious diseases, prevention and treatment of acute intestinal infections.

However revealed that the spectrum of indications for the use of probiotics in clinical practice can be significantly expanded. Thus, they found positive effects in the treatment of rheumatoid arthritis, some urinary tract infection, purulent-inflammatory complications in surgery, gynecological diseases, infectious nature, and many others.

Such diverse effects of probiotics and, in this case Biosporin determined by the original mechanism of action, which is the most complete form was justified by us.

The mechanism of therapeutic and prophylactic action of the drug Biosporin

Shortly after taking the drug starts to separate the biologically active substance and function of microbial cells, which have a direct effect on pathogenic and conditionally pathogenic microorganisms, and indirectly – through activation of specific and nonspecific protection systems macroorganism.

In the same period of probiotic bacterial cells, which may be regarded as biocatalysts of many vital processes in the digestive tract, produce active enzymes, amino acids, antibiotic substances, and other physiologically active substrates, complementary to the complex therapeutic and preventive effect.

Noting the various mechanisms of therapeutic and prophylactic effect of the preparations of the bacilli, can not claim that any of them are major, but some – of secondary importance. In various acute and chronic diseases of the gastrointestinal tract, recorded in humans and animals, the therapeutic effect in some cases can be achieved primarily through the antagonistic properties of the bacilli, in others – through the production of enzymes in the third – through the activation of protective reactions. But, as a rule, participate in the process of simultaneously taking several factors.

T.P. Lyons and R.J. Fallon called our time “coming of age of probiotics. Indeed, the rapid development of research on the development of new biological products, and further explore the mechanism of their therapeutic and prophylactic action, gives grounds to assert that in the XXI century probiotics significantly drive back to the traditional market and unsafe for the body products, especially those that apply to prophylactically.

One of the promising areas of development of new biologics is the creation of probiotics on the basis of micro-organisms with desirable properties, obtained by genetic engineering.

The first probiotic Subalin, along with high antibacterial activity against a broad spectrum of pathogens, and is characterized by antiviral activity. This drug is developed at the Institute of Microbiology and Virology. DK Zabolotnogo National Academy of Sciences of Ukraine, together with the NGO “Vector” (Russia) and is currently undergoing clinical trials with success.

Thus, the creation of probiotics and their widespread use today are a strategic direction to combat many infectious, as well as some non-communicable diseases.

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Antibiotics and / or probiotics: Thoughts and Facts
At the beginning of the century, mankind eagerly awaited new discoveries aimed at combating infectious diseases. The need for such discoveries was the fact that diseases caused by different bacteria that kill millions, as the main cause of death. So expectations were met – Alexander Fleming discovered penicillin, which experienced the most outstanding event of the first half of this century.

Discovery of penicillin was purely accidental, but it is appropriate to recall the words of Louis Pasteur that “chance is usually prepared by a certain train of thought, the fate of flashes only prepared minds.” Penicillin became known on all continents and has saved millions of lives.

Fleming’s discovery gave rise to an entirely new scientific direction, marked a new era in biology and medicine – the era of antibiotics. Their comprehensive study has enriched our understanding of the dependence of biological activity of organic compounds from the chemical structure, closer to the rational establishment of antimicrobial agents with desired properties. Example of this are the achievements in the study of semi-synthetic antibiotics.

Among the most pressing problems in dealing with antibiotics today are:

establishment and development of ways to overcome antibiotic resistance in bacteria;
explore the natural and the creation of semi-synthetic antibiotics that are effective in the fight against staphylococcal, Pseudomonas aeruginosa and other infections, malignant tumors;
search for new producers among the poorly studied groups of organisms;
study of genetic recombination in microorganisms with production of new antibiotics;
generation of new antibiotics by the directed biosynthesis and selection of appropriate mutants and recombinants.

The main problem in recent years is widely resistant forms of pathogens and reduce the effectiveness of some antibiotics. It is very telling in this regard, the study of American Scientists, showed that if people are infected with pathogens that have multiple resistance to antibiotics, the disease occurs in a much more severe, often fatal, but struggle with these illnesses more expensive.

For example, treatment of one patient with tuberculosis, in which the parasite resistance to antibiotics, costing 15 times more expensive than a patient with a susceptible agent. Thus, all the growing resistance of microorganisms to antibiotics is already costing the U.S. more than 4 billion dollars a year.

Newly ripened age-old questions – what to do and who to blame? The answer to them, to some extent, gives a result of recent studies that found that “nearly half (!) Sold in the U.S. antibiotics are absolutely not necessary. These drugs are often prescribed for colds, flu, gastro-intestinal diseases, high temperature, etc. Such a situation – it is not just a waste.

The situation is much worse, as is the spread of bacteria resistant to antibiotics, massive allergy patients, and that is very tragic, developing dysbiosis, whose frequency increases with incredible speed.

And the second – doctors prefer to prescribe the latest “strong” broad-spectrum antibiotics, instead of after the study susceptibility to apply the “old” and / or “monoline”.

Hence the answers to the questions. Who is to blame? On the one hand patients, requiring them to necessarily prescribe antibiotics for every illness, and the other doctors who are eager to respond to these requests, or are themselves the initiators of their application.

What? The most important and simple, requiring no cost – to avoid similar situations! In cases where you can avoid the use of antibiotics, you should do it, and if applied, make sure you define sensitivity (of course, except for extreme cases) to appoint alternative medications, the most harmless, but, of course, effective.

In one article it is impossible to cover widely and thoroughly all aspects of the problem, therefore, deal only with the probiotics, and specifically, on probiotics from bacteria of the genus Bacillus, which is highly representative Biosporin, developed and manufactured in Ukraine AOA “Dneprofarm” (Dnepropetrovsk).

“Probiotics” in the modern sense – a bacterial preparations of living microbial cultures that are intended to correct the host microflora and treatment of diseases. The founder of the concept of probiotics is II Metchnikoff, who in 1903 proposed the practical use of microbial antagonists to combat pathogenic bacteria.

Fundamental studies of modern biological and medical science have allowed to develop and put into practice many of the probiotics, mainly consisted of live microbial cultures. M. Vanbelle et al. (1990) define the term “probiotics” as an antonym of antibiotics, ie “promoter of life.” Probiotics, unlike antibiotics, do not adversely affect the normal microflora, therefore they are widely used for prevention and treatment dysbacterioses.

At the same time, these biological products are characterized by a pronounced clinical effect in the treatment (aftercare) of a number of acute intestinal infections. An important feature of probiotics is their ability to increase the stability of immunity of the organism, have in some cases protivoallergennoe effect, regulate and stimulate digestion. At present, medicine is already widely used laktobakterin, bifidum-bakterin, colibacterin, bifikol, atsilakt and others.

Nevertheless, throughout the world continues a lot of work to create new, more active probiotics. An important improvement of the arsenal of biological products are bacteria genus Bacillus. Properties of some strains of this group of bacteria is so versatile and attractive, that only in recent years based on them created more than a dozen effective drugs .

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Safety of paracetamol and paracetamol-containing preparations
Paracetamol (acetaminophen) – one of the most popular drugs from the group of non-steroidal anti-inflammatory drugs (NSAIDs) for symptomatic treatment of SARS and influenza. Until recently, paracetamol is considered safe drugs, their small number and a rare incidence of adverse reactions.

In recent years, data on the hepatotoxic effect of paracetamol when it is moderate overdose of paracetamol in the appointment of a high therapeutic doses, and the simultaneous admission of inducers of liver microsomal enzyme system, P-450 (antihistamines, glucocorticoids, phenobarbital, ethacrynic acid), as well as in alcoholics [1 ]. Even when receiving therapeutic doses (2,5-4 g / day), acetaminophen can cause serious liver damage in alcoholics, as well as by persons regularly consume alcohol (for men – a daily intake of over 700 ml to 200 ml of beer or wine for women – dose 2 times less), especially if paracetamol occurred within a short period of time after drinking alcohol [2]. With chronic administration of paracetamol more than 1 tablet per day (1000 or more pills for life) doubles the risk of developing severe analgesic nephropathy, leading to terminal renal insufficiency [3].

After the accident, poisoning by paracetamol in Ireland had introduced new rules for its sale. Leave with a prescription drug made in the case of the appointment of more than 50 tablets, pharmacies allowed OTC sales package containing not more than 24 tablets of paracetamol, other institutions may not sell more than 12 tablets of 500 mg or equivalent dose of paracetamol in combined preparations used for catarrhal diseases. All acetaminophen-containing products sold in Ireland, should contain the following label: “Contains paracetamol, as well as warnings -” Do not take other paracetamol-containing products “,” In case of overdose seek immediate medical help, even if you feel normal, due to the high risk of irreversible liver damage. Please read carefully the instructions on the application “[4]. Less stringent rules imposed sale of paracetamol in the UK, where a prescription is required only if you buy more than 100 tablets [5].

In Russia, paracetamol before the end of 1998 was resolved as a prescription drug in a daily dose of 2 g, whereas in many European countries and the United States paracetamol was used as OTC drugs in a daily dose for adults 4 g [6]. In September 1998, Moscow hosted an international symposium, “The efficacy and safety of paracetamol, in which it was decided to apply to the State Pharmacological Committee (PGA) to consider changing the OTC daily dose of paracetamol in the direction of its increase to 4, the Special Commission PGA of Toxicology, Pediatric Gastroenterology and consider the use of paracetamol as a prescription drug. Based on the findings of the commissions recommended the PGA in the instructions on paracetamol-containing products following additions:

a) The maximum dose of paracetamol for a non-prescription medicines in children – 10-15 mg / kg every 8 hours, taking as a febrifuge no more than 3 days, as a painkiller – not more than 5 days;

b) The maximum daily dose of paracetamol for prescription medicines in adults 4 g;

c) All known contraindications and warnings for paracetamol;

g) “abusers of alcohol before taking this medication should consult a doctor. Paracetamol may have a damaging effect on the liver “[7].

It should be borne in mind that acetaminophen is contained not only in the preparations of the same name or business analogs, but also part of the combined drugs. Therefore always necessary to consider the dose of paracetamol in the appointment of combined paracetamol-containing preparations to avoid overdose.

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Acomplia
	Acomplia (Rimonabant) is an appetite suppressant diet pill.

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Resource for consumers to help them make better buying decisions when shopping online. Rimonabant 20mg Buing Online Guide. Order Cheap Medications Online.
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Acomplia
	Acomplia (Rimonabant) is an appetite suppressant diet pill.

	Package	Price	Per Item	Savings	Order
	Acomplia 60 pills x 20 mg	$53.12	$0.89	$0
	Acomplia 90 pills x 20 mg	$69.45	$0.77	$10
	Acomplia 120 pills x 20 mg	$82.55	$0.69	$24
	Acomplia 180 pills x 20 mg	$115.13	$0.64	$45
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