Calm, only calm!

Sedative medications (Latin sedativo - "soothing") are a group of drugs of plant and synthetic origin that cause calming or reducing emotional stress without a hypnotic effect. However, at the same time, they facilitate the onset of natural sleep and deepen it.

In the retail market of sedatives, more than 40 medicines are produced by more than 140 corporations. The greatest demand for drugs in the form of oral drops, tablets and tinctures.

Top 5 most popular drugs in both value and in-kind led Corvalol (more than 30 manufacturers). The second place in the rating in terms of value is Novo-Passit (Teva Pharmaceutical Industries Ltd), III - Valerkordin (Krewel Meuselbach GmbH), IV - TM Persen (Novartis). Closes the top five leaders Valeriana extract (more than 10 producers).

At the footsteps of Meldonium

110 positive samples: who is to blame and what would be

Scandal associated with the use of Russian athletes banned Meldonium, overgrown with new details. Each of the caught adheres to a certain tactic of behavior: one publicly repents, the other declares the fact of throws the drug, the third explains the use of Mildronate disease, and finally the latest version - a secret conspiracy against the Russian team. However, experts said unequivocally: that Meldonium was included in the list of banned drugs, sports doctors knew long before the official announcement of this fact. The fatal miscalculation is that everyone blindly trusted the instructions, which indicated the timing of removal of the substance from the body. They were too far from reality.

The habit of using Meldonium

The drug Mildronate firmly entered the sports of domestic medicine in the period 1988-1993. The peculiarity of its reception consisted in a rather long cyclicity - from 21 to 42 days 3-4 times a year. But until now it is very difficult to talk about its effectiveness or inefficiency. This was discussed during the meeting of the debating club of the First Moscow State Medical University Sechenov said the deputy. head of the sports medicine organization of the Federal Medical and Biological Agency (FMBA) Tatyana Pushkina. She stressed once again that the doctors of the sports team of the Russian Federation were repeatedly informed about the introduction of Meldonium into the list of prohibited preparations. Do not deny this and the doctor of the men's soccer team Eduard Bezuglov: "Everyone knew about this, even my cat."

In addition, as it turned out, WADA made a request for an expert evaluation of the inclusion of Meldonium in the black list. At least, the presence of such an appeal was confirmed by the member of the Medical Committee of the International Paralympic Committee, Guzel Idrisova. "Back in June, WADA asked to give expert assessment to the drugs listed, including Meldonium. We expressed doubts about the need for this, said that it is accepted by our athletes, but does not give them any sports advantages, "she said. But it should be taken into account that this is the opinion of a separate committee, whether Russia's position has been officially presented in WADA, is still unclear.

Child without an eye
The opinion of experts participating in the meeting of the club, who is to blame for what happened, is unequivocal: athletes. According to representatives of the FMBA, the issuance of Mildronate to the team doctors ended in mid-October. But the organization can only be responsible for full-time medical workers. If an athlete resorted to the services of a personal doctor - this is no longer a problem for FMBA. "The WADA Code clearly states that the athlete himself is responsible," Eduard Bezuglov reminded, saying that he never appointed Mildronate to his charges.

White crow

Perhaps the most interesting fact of this story - meldonium is included in the most severe class of banned substances S4. Its "neighbors" - for example, hormonal drugs, which are used to increase muscle mass. The peculiarity of Mildronate is that there is no absolute evidence base for its effectiveness. "It was not possible to get data on the fact that meldonium improves sports performance," - said the head. Department of Sports Medicine and Medical Rehabilitation of the First Moscow State Medical University Sechenov Evgeniy Achkasov. When asked why, then the athletes took it, and even so cyclically and often, the professor of the Department of Nervous Diseases of the Medical Faculty of the First Moscow State Medical University. THEM. Sechenov Vladimir Zakharov replied: "When we say that the effectiveness of a given drug is not absolutely proved, it does not mean that it does not work."

Stuck in the blood
The devil, as you know, lies in the details. In the box with Mildronate, of course, there is an instruction in which the terms of complete elimination of the substance from the body are written in black and white. Based on these data, by simple mathematical calculations, it is likely that doctors or the athletes themselves were confident that they have enough time to submit doping tests. However, WADA dug very deeply, much deeper than the clinicians 30 years ago. That is why the results of the tests turned out to be paradoxical.

"Now anyone you ask, whether using Mildronate, will answer: no. The brush is ready to be chopped off. But in fact, he did it yesterday or even now in his pocket is the medicine. Many doctors, opening the annotation, sincerely believed that in 3-4 days everything would come out. So let the tales not tell, "Eduard Bezuglov categorically noted.

At the moment, FMBA initiated a study of Meldonium with the aim, first, to obtain more reliable data on the real time of drug withdrawal, and second, to prove to WADA that its use did not affect sports results. Then there is the hope that the Meldonium will be excluded from the list of doping drugs. According to Andrei Sereda, director of the Federal Scientific Center for Sports Medicine and Rehabilitation of the Federal Medical and Biological Agency of Russia, the primary study conducted by the agency showed that the withdrawal period may be about six months. And maybe more. In the near future FMBA promises to publish data for the month. But even now experts say that the rate of excretion affects the sex and even the nationality of a person.

What will end this story is unclear. To date, there is only a statement of fact: 110 positive doping tests at meldonium. The screening continues. On what sanctions will be applied against Russian athletes, WADA does not hurry to make a statement.

Tablets for memory

This review examines the dynamics of pharmacy sales of drugs registered in the WHO classifier N06B, "Psychostimulants, agents used for attention deficit disorder, and nootropic drugs." In this group, both medicines obtained by the chemical synthesis method and preparations from animal raw materials and plant origin are presented. The volume of pharmacy sales of N06B drugs for 9 months was $ 203 million, or 40 million packs.

The drugs of the group are in stable demand; their pharmacy sales are not subject to seasonal fluctuations. The share of nootropics and psychostimulants is more than 2% in the total volume of pharmacy sales in value terms (they are only ahead of such groups as analgesics, antipyretics, immunomodulators, NSAIDs and anticongestants). Nootropics are usually used for long courses, so pharmacies have the opportunity to purchase loyal customers in the face of consumers of this group.

In the group of nootropics and psychostimulants, more than a third of sold drugs in value terms - domestic production (in the total pharmacy sales, the share of Russian products is one-fourth). It's like traditional preparations Piracetam, Vinpocetine, Caffeine - sodium benzoate, and innovative products Cortexin, Phentotropil, Semax. In physical terms, the ratio of sales volumes is even more biased towards domestic drugs because of their greater price affordability compared to imports.

The share of drugs in the price category over $ 70 made up almost 50% of the total pharmacy sales in the analyzed period. In this price category came the drugs Cogitum, Encephabol, Noben, Semax. As a result of the increase in the price, a new Strattera drug entered this category, sales of which began in 2007. Sales of psychostimulants and nootropics are cheaper than $ 25. This category includes generic generics, which are in greater demand in hospital purchases, where the price of preparations is decisive, rather than in the commercial retail sector, where the consumer trusts branded drugs more.

Pharmacy sales of N06B drugs from hospital purchases are significantly different and structure by form of release. If in the commercial retail sector drugs predominate in the forms of release for internal use - tablets and capsules, in the hospital sector the traditional for the hospital forms of injection - injection and infusion ones prevail. Currently, the drugs of the group are actively used in the provision of emergency care, as well as in the rehabilitation period.

In the rating of manufacturers of psychostimulants and nootropics, the Gedeon Richter Corporation is the leader, with Cavinton (99%) dominant in sales. Among the domestic producers, the "Valenta" is leading, having a balanced portfolio of products of the analyzed group (Phentropil, Pantocalcin, Vinpocetin, Pantogam, Pyracetam, etc.). Pharmacy sales of "Valenta" grow at the highest rates, therefore this manufacturer has the opportunity to significantly increase its share of the presence in this sector of the pharmaceutical market.

The traditional sales leader among the group's drugs is Cavinton (17.53%), which has a lot of indications for use. Not inferior to the position and the founder of the group Nootropil with a market share of 7%. The increase in sales is led by the domestic drug Phentropil ("Valenta", market share - 8%, sales increase - 55%). Of the drugs not included in TOP10 during the period under review, but having all the prerequisites for replenishing the rating table in the near future, Bilobil, a herbal preparation based on ginkgo biloba, attracts attention.

The pace of life of a modern person is growing every year in a geometric progression; the amount of information that needs to be processed also increases, and the load on the nervous system and the brain. As a consequence, the need for drugs that without side effects help people cope with the daily workload will only grow. The general aging of the population also contributes to the positive dynamics of sales of nootropics: in fact, older people are the main consumers of these drugs.

TOP 10 nootropics
1) Cavinton
2) Cerebrolysin
3) Tanakan
4) Cortexin
5) Phenotropil
6) Nootropil
7) Fezam
8) Pyracetam
9) Pantogam
10 Vinpocetine

Radiculitis

Lumbosacral sciatica, or radiculopathy - is one of the most common causes of back pain. Radiculopathy underlies the development of pain syndrome, characterized by intense pain, accompanied by a restriction of mobility and determines the high incidence of incapacity. Pain caused by radiculopathy is experienced by 3-5% of people at one or another age. However, in men, sciatica occurs more often at the age of 40-50 years, and in women - at 50-60 years.

Risk factors for the development of radiculopathy:
- occupation by heavy physical labor;
- smoking;
- heredity.

Causes of lumbosacral radiculopathy:
- degenerative-dystrophic changes in intervertebral discs (eg, herniated intervertebral disc);
- tumors;
- Infectious and inflammatory diseases of the spine;
- congenital anomalies;
- endocrine and metabolic disorders.

Symptoms of sciatica:
- pain in the back (shooting or piercing), which can reach the foot, sometimes to the knee, sometimes to - the middle of the shin;
- weakness in the leg or foot;
- loss of temperature, vibration and pain sensitivity.

Consequences of sciatica:
- weakness and saggy foot;
- loss of leg muscle mass;
- numbness and hyposeusia of the perineum;
- violation of the pelvic organs - delay or incontinence of urination, incontinence of stool.

General medicines:
Non-steroidal anti-inflammatory drugs of oxycam: Matarin plus, piroxicam, Tenikam, Tilkotil, Tobitil and others.

Non-steroidal anti-inflammatory preparations of pyrazolones: Pentafuphene, Piralgin, Sedal-M, Analgin, and others.

Non-steroidal anti-inflammatory preparations of propionic acid derivatives: Dexalgin, Dexalgin 25, Brufen SR, Dolgit, Ketonal, Ketoprofen Organica, Febrofide, Flamax forte, Nalgezin Fort, Dip Rilif, Ibuprofen, Ibusan, Bystrumgel, Fastum gel, Flexen, Naprios,

Nonsteroidal anti-inflammatory drugs derivatives of salicylic acid: Bom-Benge et al.

Non-steroidal anti-inflammatory preparations acetic acid derivatives: Voltaren, Voltaren Emulgel, Klinoril, diclofenac, Naklofen, Rapten Duo, Ketanov, Ketorol, ketorolac, Dicloran plus, Eftimetacin, etc.

Non-steroidal anti-inflammatory drugs Fenamates: Revmon Gel, etc.

Non-narcotic analgesics, including non-steroidal and other anti-inflammatory drugs: Nektrim Active, Citralgin, Nyz, Nimulid, Deep Heath, Arthro-Active balm oil warming, Gumizol, Thermo-rheumont, Nifluril, Cathadolon Fort, Alorom and others.

m-, n-holinomimetics, incl. anticholinesterase drugs: Nivalin, Aksamon, and others.

Local irritating agents: Apizartron, Badyaga, Perkamf, Pepper tincture, Provinenol, Forapin E, Espol, Ungapiven, Kapsikam, Nayatoks, Efkamon, Pepper plaster, Viprosal B, Betalgon, Bethanicomylon and others.

Glucocorticosteroids: Ambien et al.

Additional medicines

Angioprotectors and correctors of microcirculation: Aescin, Reparil-gel H, etc.

Vitamins and vitamin-like drugs: Pyridoxalphosphate, Milgamma compositum, Compligam B, Milgamma, Thiamine chloride, cyanocobalamin, Neurobionum, Benfolipen, Neuromultivitis, Endur-B, etc.

Dermatotropin funds: Dimexid and others.

Homeopathic remedies: Radiculosan, Revma-gel, etc.

Correctors of bone and cartilage tissue metabolism: Vitreous humor, etc.

Means that affect the neuromuscular transmission: Myolastan, Sirdalud, and others.

Other drugs: medical plaster DORSAPLAST, etc.

Frost - white nose

It's so difficult to stay at home on New Year's Eve! Someone goes to the square to the city tree, someone goes to ride on the hill, someone just walks around the guests ... And yet not everyone sees in time how the fingers, ears, edges of the cheekbones, the tip of the nose, whiten and lose sensitivity . Meanwhile, this is the first sign of the beginning of frostbite - and at this stage, competent first aid is needed.

What can I freeze?
Frostbite (or frostbite - this term is considered by many to be more correct, but it is too ambiguous in the current colloquial speech ...) - this is a skin lesion under the influence of low temperatures. In some ways, it is similar to a burn and also refers to thermal injuries - but if the direct effect of high temperature on living tissues is of primary importance in burns, the mechanism of frostbite development is different. As you know, a person is warm-blooded, so even in cold weather our skin is "warmed" from the inside by the heat of our body, the frost and wind in this case damage (air) only the epidermis - the uppermost layer in contact with cold air. In deeper layers, the network of blood vessels plays the role of a heating system - the blood constantly enters the skin, gives it some of its heat and leaves to "warm up" in other parts of the body. If a person is dressed for the weather and comfortable, his face and hands are noticeably cool.

However, frostbite can also be something that is closed by clothing and especially shoes - even in winter boots or boots, the toes and feet as a whole may suffer, everyone knows well what "icy" and whitened they can be. Do not save and warm, thick socks, which can be worn even polar boots. Moreover - sometimes the thickness of socks is superfluous and harmful. The shoes become tight, the fingers lose mobility, the foot is tightly compressed - and the circulation of blood in the capillaries begins. The heating system "turns off", the legs gradually cool, the vessels from the cold narrow even more, insufficient blood supply and disruption of innervation lead to oxygen starvation of tissues, and this threatens them with necrosis...

Do not rub the frosted area with snow, coarse woolen cloth, etc. - at the same time, microtraumas, cracks and scratches are formed through which an infection can enter the weakened skin.

The same happens in open areas of the skin under the influence of frost, especially with the wind: the blood vessels contract from the cold, the circulation is disturbed - this is evident by the way the skin turns pale and white. This is the first stage of frostbite - the easiest, without deep lesions of the skin and especially lying below the tissues.

It should be noted that it is possible to frostbite even at an air temperature above zero - up to + 8 ° Ñ. Closely and wet clothes and shoes (lost their heat-protective properties), prolonged immobility, general weakening of the body, alcoholic intoxication (with its expansion after blood vessels contraction), strong wind, high humidity - the more such predisposing factors, the more "warm "There may be conditions in which a person can frostbite hands, feet and face.

Down in degrees ...
At the first degree of frostbite, impaired blood circulation leads to a feeling of numbness and tingling, whitening of the skin, with warming alternating red and crimson color and swelling, burning, sometimes very painful. If the frostbite place was heated quickly and correctly, the damaged tissues are restored within a week, after peeling of the frozen epidermis and the growth of a new layer. However, tenderness in the cold can last much longer.

More severe frostbite is similar in appearance to a burn: on the 2nd degree the affected skin is covered with bubbles with transparent contents, itch and it hurts, the healing may take up to 2 weeks. Prolonged exposure to cold leads to the third degree of frostbite - deep necrosis, the blisters become bloody, the skin darkens and flakes in the affected areas, scars form during healing (which takes more than a month). The heaviest, IV degree is the dying not only of the skin, but also of the underlying tissues, the skin completely loses sensitivity, the affected area swells from the swelling and turns black.

Particular danger is the transfer of decay products from dying tissues throughout the body - this leads to general intoxication and worsening of the condition of the victim. In such cases, sometimes you have to resort to surgery and excise the affected areas, and sometimes amputated frostbitten fingers, feet or brushes.

How to help?
The very first help that can be given to a person who has been frostbitten is to tell him what is happening: because of loss of skin sensitivity a person may not notice signs of frostbite. So if someone from the people who have met in the cold on the street or who went behind the shopping in the pharmacy turned white ears, the tip of the nose, the corners of the cheekbones, pay attention and advise what to do!

With frostbite of the I degree it is quite possible to cope independently, and it will pass with minimal consequences. It is necessary to warm the affected area, and even better - and the injured. Take him to a warm room, pour hot tea. Frozen skin should be warmed with warm hands - while only light massage is allowed, but not vigorous rubbing! With a cold lesion, the walls of the vessels become brittle, easily damaged. Do not rub the frosted area with snow, coarse woolen cloth, etc. - at the same time, microtraumas, cracks and scratches are formed through which an infection can enter the weakened skin. But a sterile cotton-gauze dressing or a warming compress will be quite appropriate, as well as a tablet of NSAIDs, which reduces pain, swelling, etc.

Heating baths with frostbite and hypothermia should not be hot - they will increase the severity of the lesion. If it is necessary to warm the victim in water, the temperature should be increased gradually from room temperature (24 ° C) to body temperature or slightly higher (37-38 ° C).

It is not recommended to warm up the injured limbs in the heater, the heating battery, especially at the open fire: the sensitivity of the frost-bitten tissues is reduced, and a person may not notice how he will get another thermal trauma - a burn.

Rubbing alcohol solutions, fat-based ointments, oils is sometimes permissible at I degree of frostbite, but the problem is that it is not immediately and not always possible to determine more severe degrees when such drugs are contraindicated. It is best to postpone the local preparations before the onset of skin peeling. She will come a few days after the injury. And then you may need moisturizing and nourishing creams, or even better - water based gels. There are ointments and balms, specially designed for the treatment of frostbite, but they are not always recommended to apply immediately - you must first carefully read the instructions! And, of course, it is unacceptable to use special "winter" cosmetics, not intended for treatment, but for the prevention of frostbite - it should be applied to healthy, not damaged skin.

If the frostbitten person warms up not at home, but at work, at a party, in an accidental warm place (for example, in a drugstore) and then must go out again to frost, you need to protect the affected area from the cold air and advise you to call a taxi: they do not save on health, but re-cooling of the newly "saved" area can lead to more severe tissue damage.

In some cases, instead of a taxi, you need to call an ambulance. The sites of frostbite of the 2nd degree should be processed by professionals in aseptic conditions, and the heavier ones require immediate hospitalization and specialized medical care. Deep cold tissue lesions, including necrosis, may not appear immediately, so if there is severe frost, prolonged hypothermia, a rapid (already frosty) bubble formation, one must suspect a heavier degree of frostbite than it seems at first glance!

Viral infections: what's in the arsenal?

What medicines are most in demand at the end of winter - early spring? Of course, the whole arsenal of anti-cold means: there is a seasonal epidemic of flu and ARVI, so that - cough, runny nose, headache ... Alas, most of the drugs prescribed and bought "from cold" are struggling with these symptoms, and not with the very cause of the disease is viruses. And what do we have with the minority, i.e. with antiviral drugs?

How to defeat the infection?
The first "line of defense" in the fight against viral infections is vaccination today.

If the infection is caused by bacteria, everything is simple enough: most microbes are susceptible to certain antibiotics, you just need to pick the right one and apply it correctly, without disturbance and with constant monitoring. With viruses, everything is much more complicated: they are insensitive to antibiotics, special antiviral substances often act only on certain types (and even individual strains) of the causative agents of the "cold", and those because of their high variability can quickly adapt to the active substance, to react to it. Therefore, in the prevention, and treatment of acute respiratory viral infections or influenza, there are no single universal tools - at least a few, but which will definitely fit anyone and cope with any virus.

The first "line of defense" in the fight against viral infections today is vaccination: experts predict the spread of viruses of certain strains, based on this forecast, a vaccine is created - and even if doctors have not guessed the strains, many vaccinated people are less likely to develop influenza, Immunity is already ready to face the virus. Unfortunately, not all are vaccinated, and vaccination itself comes only from the flu. From adenoviruses, PC viruses and many other pathogens of acute respiratory viral infection, which can give the majority of cases of "colds" during a seasonal epidemic, this vaccination does not help. And, of course, vaccination works only as a preventive, prophylactic measure and only for a healthy organism - if the first symptoms appear, it is too late and even harmful to plant. Both for prophylaxis and for treatment of acute respiratory viral infections, preparations of interferon - a specific protein (more precisely, a group of proteins), produced by our body in response to the penetration of viruses into it, are widely used. The action of interferons is indiscriminate, so they show activity against most viruses (and strains) that cause influenza and ARVI, but do not destroy the viruses themselves, but activate the immune system, increasing the resistance of cells and suppressing the multiplication of pathogens in them. In addition to preparations containing interferons themselves, inductors that enhance the synthesis of these proteins by the body are also used-such drugs are referred to as immunostimulants.

However, in severe forms of the disease, our immune system can not cope with the "invasion" of viruses even after taking stimulants, and in this case, drugs that directly suppress the development of the pathogen are needed - etiotropic antiviral agents.

All viruses are different ...
Antiviral drugs are not so few, but not all of them will act on the viruses that cause ARVI. For example, acyclovir, effective for fighting the causative agents of herpes, chicken pox, shingles, will be virtually useless against influenza viruses: it acts on DNA-containing viruses, and influenza causes RNA-containing. And even for drugs intended for the treatment of influenza, the effectiveness against very common pathogens ARVI, for example respiratory syncytial (PC) virus or adenoviruses, may be insufficient or not observed at all. Therefore, when selling such drugs, it is advisable to check with the buyer whether the diagnosis was "influenza" by a specialist or, as we often do, the patient with an easy cold decided that he "zippipoval", and is going to undergo treatment independently ...

And even against influenza viruses, the effectiveness of different drugs can be different - depending on whether it is a virus, A or B, sometimes even from a specific strain. Moreover, many antiviral drugs have quite pronounced side effects, so without an accurate definition of the pathogen and the appointment of a doctor, it is better not to take them: they can act less on a "cold" than on the patient's body!

Umifenovir acts on influenza A and B viruses, is used to treat rotavirus infections and is low-toxic, relatively safe (it is not prescribed only to pregnant women, children under 3 years of age and in cases of hypersensitivity to the drug).

It reduces the duration of an acute period of the disease and reduces symptoms of intoxication. It should not be an independent and unique means of "flu" (as well as other antiviral drugs) - complex treatment is necessary, in which this drug will be only one of the prescribed medicines.

Oseltamivir is intended for the treatment of influenza A and B, but it is ineffective for ARVI caused by other diseases, and even for the treatment of influenza B it is necessary to achieve a higher concentration than when fighting the influenza A virus - so this drug can be considered highly specialized, "influenza ". Specialists prescribe it only in severe cases confirmed by laboratory tests of influenza, as a preventive drug this drug is not prescribed at all, and in mild cases, possible harm may outweigh the benefit. The fact is that this remedy is considered toxic (it is especially noticeable when treating for a long time on the kidneys and nervous system) and can cause undesirable side effects from insomnia to coughing, headache and nausea - i.e. with improper application or individual intolerance itself can cause symptoms similar to influenza and ARVI! In this regard, mass purchases that began a few years ago on the recommendation of the WHO, are currently suspended by several countries, the application is limited and additional studies are conducted on the efficacy and safety of the drug. In addition, more strains resistant to oseltamivir have recently been detected.

Rimantadine is a part of various drugs and has been used for the prevention and treatment of influenza since the 1960s. A great clinical experience of its use has been accumulated, many studies have been carried out, but such a long application has led to the formation of a significant number of strains resistant to this substance. In addition, rimantadine is effective only against influenza A viruses - it does not affect other pathogens of influenza and SARS. Its effect (if the strain is sensitive to the drug) is quite effective, there is a noticeable relief of symptoms and a reduction in the total time of the disease, but for such successful treatment, precise diagnosis is necessary with isolation of the pathogen and its test for resistance to rimantadine, but independent use against "cold" can and have no effect on the course of the disease. Long-term experience with rimantadine has allowed us to identify numerous contraindications-not only pregnancy and children under 7 years old, but also many chronic liver, kidney and cardiovascular diseases: for elderly patients with hypertension, it is not recommended because of the danger of development hemorrhagic stroke.

SARS, influenza, even with a light current are fraught with sudden complications, affecting a variety of systems and organs, so do not try to "move on your feet" viral infection and even more so you can not self-medicate in severe cases.

Vitaglutam, or imidazolylethanamide pentanedioic acid, is recommended for the treatment of a wide variety of viral diseases: influenza A and B of any strains, adenovirus infections, parainfluenza, infections caused by the PC virus. In addition to antiviral action, it also has anti-inflammatory and immunomodulatory effects. However, as with many other drugs, radical and rapid cure after its administration is not expected - the period of fever is shortened, the symptoms of intoxication and catarrhal symptoms decrease, the overall duration of the disease may decrease and the probability of complications after the illness may decrease.

The merits of this drug include low toxicity - of the expressed side effects only occasionally, in cases of individual intolerance, allergic reactions are noted. But still it is not recommended for pregnant women, nursing mothers and children under the age of 18, and the dosage and duration of treatment, like other antiviral drugs, should be determined by the attending physician.

What else?
Of course, in this short review, it is simply impossible to cover the entire market of the funds offered to combat viral "colds" - hundreds of names of preparations of the most diverse groups. Someone prefers homeopathic remedies, some - vegetative immunomodulators, many choose complex anti-catarrhal drugs - their action is mostly symptomatic, but in light cases and it is enough to ease your well-being, and then the body copes with the viruses on its own ...

However, it should be remembered that the "usual" ARVI, and especially the flu, even with a light course are fraught with sudden complications, affecting a variety of systems and organs, so in any case, do not try to "move your leg" virus infection and even more so engage in self-medication in severe cases: if effective antiviral drugs are required, only a doctor should prescribe them after the diagnosis has been clarified and all contraindications taken into account!

Stomatitis. Not so simple...

Many people get acquainted with stomatitis even in infancy, then from time to time the illness reminds oneself - and so on until the very old age ... This disease has many kinds and forms that unite, perhaps, two common features: first, the location of the foci disease, and secondly, the fact that without the help of specialists completely and reliably cure it will not work.

Everything in the mouth
Most common infectious stomatitis, and the causative agents can be a variety of microorganisms from viruses to fungi.

The term "stomatitis" refers to the lesion of the oral mucosa. Previously, it was believed that stomatitis - an inflammatory disease, it was now found that not all of its forms are directly related to inflammation, in some cases this condition can be caused by an immune (and autoimmune) reaction. Usually, stomatitis as such is said in case of extensive lesions affecting different parts of the oral cavity, however, for the same reasons and symptoms, depending on the localization of the problem, a diagnosis can be made of "cheilitis" (if the lesion is located on the lips), "palatinitis" (the disease affects sky), glossitis (the focus is localized on the mucous membrane of the tongue), and finally, one of the most common types of stomatitis is gingivitis, gum lesions.

The main factors contributing to the development of stomatitis are the weakening of the immune system due to illnesses, stresses, vitamin deficiency, etc., infections and trauma. And the sources of injuries can be very different - from calculus, irritating and damaging the gum, to too hot or too spicy food, resulting in thermal or chemical burns of the mucosa. Untreated in time diseases of teeth and gums, substandard, not fitted, etc. dentures, even improper cleaning of teeth - all this can lead to the development of some form of stomatitis.

The easiest form is catarrhal stomatitis, with it the mucous membrane of the oral cavity becomes painful in some areas, reddens and swells, the patient feels dryness and burning sensation in the mouth. Catarrhal stomatitis can appear for a variety of reasons, from burns to infections. Very often it is in the form of catarrhal allergic stomatitis, which can cause both food allergens, and any drugs. This form is considered the easiest, with no significant damage to the mucosa, and with timely proper treatment, stomatitis usually passes quickly and without consequences.

In this case, acute herpetic stomatitis can proceed quite heavily, with a rise in temperature to 39-40 ° C, and requires a multi-day treatment.

When fibrinous, or aphthous stomatitis on the mucous membrane, characteristic defects - aphthae, small round or oval ulcers with redness and swelling around the damaged area are formed. Aphids originate from small vesicles and sometimes remain covered with a film; therefore, with aphthous stomatitis, another form is sometimes confused: vesicular stomatitis, which is characterized by the formation of vesicles-point bubbles opening up during mechanical injuries (for example, when chewing food). The nature of aphthous and vesicular stomatitis is different (vesicular usually develops with viral infections), accordingly, treatment will be different, so that errors in diagnosis can greatly complicate the appointment of the right treatment.

And mistakes in treatment are fraught with the transition of stomatitis to ulcerative, or gangrenous - this is the heaviest form with extensive and profound lesions of the mucous membrane, passing to neighboring tissues. Usually ulcerative stomatitis is observed with weakened immunity and develops as a consequence in time of not cured acute stomatitis or as an exacerbation of a chronic disease.

Let's look at the reasons
In order to cure stomatitis (like any other disease), you need to know exactly its cause. The easiest way is in cases of traumatic stomatitis - damage to the mucous membrane with a stiff piece of food, bite of the cheek or lip, burn, etc. are usually felt immediately, and the place of damage is remembered well, and a poorly fitted denture makes itself felt in the most unambiguous way. After the injury, of course, its cause is often not eliminated (although in the case of a tartar or an interfering prosthesis it is possible and necessary to immediately go to the dentist), but you can reduce the risk of unwanted consequences by treating the injury site with an antiseptic and continuing this treatment regularly until complete healing. If the measures are taken in a timely manner, stomatitis either does not develop at all, or passes in mild catarrhal form, but the continuation of permanent trauma and infection of the wound can lead to the formation of ulcers and ulcers, which will be cured much more difficult.

Most often, stomatitis is infectious, and pathogens can be a variety of microorganisms - from viruses to fungi. Viral stomatitis often develops as a complication of more extensive virus infections - influenza, measles, etc., and usually occur in a vesicular form, in which case it is not necessary to understand the cause of stomatitis simply and separately, except for the already prescribed antiviral and immunomodulatory therapy . But stomatitis caused by herpes viruses or human papillomaviruses, are often chronic, repetitive, and this is an occasion for examining the immune system: in order to prevent the development of such a disease, natural body protection is sufficient, and relapses indicate its weakening. In this case, acute herpetic stomatitis can proceed quite heavily, with a rise in temperature to 39-40 ° C, and requires a multi-day treatment.

Bacterial infectious stomatitis is also often caused by the same microbes that affect the mucous membrane of the respiratory tract, eye, etc. - stomatitis may be accompanied by diphtheria, scarlet fever, gonorrhea, streptococcal and staphylococcal infections. Most often this also occurs against a background of decreased immunity, in addition, bacterial infection can be secondary, developing at the site of damage to the mucous membrane in trauma, vesicle opening, etc. Bacterial stomatitis usually occurs in aphthous, and started - in ulcer form, and the appearance of aphthae is possible even with a mixed allergic-infectious form of the disease, so that in addition to identifying the pathogen and taking antibiotics, consultation with an allergist and complex treatment may be required.

With long-term treatment (and especially self-medication) with antibiotics and reduced immunity, fungal (usually candidal) stomatitis often develops.

With long-term treatment (and especially self-medication) with antibiotics and reduced immunity, fungal (usually candidal) stomatitis often develops. However, it also occurs as an independent infection. With candidiasis stomatitis, the mucous membrane not only dries, hurts and blushes, but is often covered with a white, curdled coating with an unpleasant "sour" smell. For treatment, usually not only antifungal drugs are prescribed, but also immunostimulants.

In special groups, stomatitis is symptomatic and specific. Symptomatic stomatitis of this or that nature arises as a consequence of various general diseases, which are not directly related to the oral cavity, such as vascular diseases, nervous, endocrine, and even abnormalities of the digestive tract. Often, symptomatic stomatitis is mild, the patients do not pay much attention to it and do not go to the doctors. But experts in such cases usually are alarmed by the ineffectiveness of the usual treatment of mild catarrhal stomatitis, and they can refer the patient for examination to other doctors, as a result of which serious chronic diseases that a person could not suspect were revealed.

Specific stomatitis occurs under the influence of certain external factors, for example, taking medications (medicinal stomatitis), penetrating radiation (radiation stomatitis), poisoning with various chemical substances (toxic stomatitis), some cases of stomatitis development in case of severe systemic diseases - syphilis, tuberculosis, etc.

How and what to treat?
We are used to treating a dentist with complaints of toothache. However, with all suspicions of stomatitis, it is necessary first of all to go to this specialist, without waiting for the large purulent ulcers to grow from small spots. Further, it is likely that other doctors will also have to undergo a screening - in search of the cause of the disease, which may not be covered in the oral cavity, and normal, complex, systemic treatment, which can include a variety of procedures (with stomatitis often prescribed and physiotherapy) and drugs - from vitamin-mineral complexes to broad-spectrum antibiotics.

But special attention, of course, will have to be given to various local remedies for antiseptic treatment and anti-inflammatory therapy in the oral cavity. Their choice is now quite large - they are herbal preparations (usually herbal extracts and the like for rinsing), and soft forms - gels, ointments, creams for application to mucous membranes, and aerosols with antiseptics, antibiotics and the means creating a protective film on the affected areas. Some drugs used to treat colds may also prove useful. This is primarily lollipops, lozenges, resorption tablets that have a complex effect - antiseptic, anti-inflammatory, analgesic.

It is necessary to use medicines quite often - at least after each meal it will be necessary to carefully process the oral cavity, so that the food remains do not irritate the painful areas and do not create a breeding ground for the reproduction of bacteria and fungi. By the way, in the diet, there can be changes: for successful treatment of stomatitis, you must give up acute, salty, sour, dry, hot food - in short, anything that can affect the mucous membrane too much. Usually, preference is given to boiled, steam and ground foods with increased amounts of vitamins and reduced carbohydrates. And, of course, we must not forget about the means of caring for teeth and gums: even if stomatitis is localized in other areas of the mucosa, it can spread to the gums, it is generally one of the most vulnerable places in the mouth. Therefore toothbrushes, pastes, elixirs for rinsing should become the topic of a separate conversation with the dentist, and it is possible that during the treatment it will be necessary to use special means for more gentle cleaning and additional protection of the soft tissues of the oral cavity.

Trophic ulcers: a complex problem without simple solutions

The problems associated with the occurrence of ulcers on the skin, worries humanity for more than one century. And, unfortunately, it is still impossible to completely solve them. Moreover, in our time, issues of treatment and prevention of such a violation as trophic ulcers become more urgent. This is primarily due to the growing number of vascular diseases, leading to blood flow disorders. So, in the USA and Western Europe, up to 25% of the population suffer from one or another form of varicose veins. In general, chronic venous insufficiency (CVI) of the lower limbs - one of the main causes of the appearance of trophic ulcers - is observed in about 10-15% of the adult population of the planet, in developed countries this figure is increased to 20%. In Russia, the same picture is observed - about 38 million people suffer from CVI, recently there has been an increase in the incidence, and about 5 million people have trophic ulcers, mainly feet and shins.

What it is?
A trophic ulcer is a defect in the skin or mucous membrane, as well as under the tissues located under them, resulting from a disturbance in their normal nutrition, most often due to a deterioration in the blood supply, or, more rarely, of nervous trophism. These disorders can lead to various diseases and injuries, but the result is a violation of microcirculation in this or that area of the skin with subsequent necrosis of soft tissues. The dead part is rejected, and an ulcer is formed on the skin - chronic, long (months, and sometimes even years), not healing, after healing prone to re-opening. In addition to complicating the situation (up to sepsis), infection of ulcers by various microorganisms can occur and is relatively rare (up to 3.5% of cases), but extremely dangerous cancer degeneration of trophic ulcers.

More than half of the trophic ulcers - 52% - occur as a result of varicose veins, 7% - with thrombophlebitis CVI, 14% of trophic ulcers - "arterial" origin, and they arise as a result of chronic arterial insufficiency, for example, with obliterating atherosclerosis. Mixed violation of blood supply (when both venous and arterial insufficiency develop simultaneously) gives 13% of cases of trophic ulcers. Post-traumatic ulcers (resulting from infection of wounds, burns, frostbite on the ground, etc.) account for 6% of the total statistics, neurotrophic (resulting from a non-blood supply, and nervous trophism - for example, spinal injuries that cause nerve impulses and loss of sensitivity in any zone) - 1%. A special problem is considered to be diabetic trophic ulcers (5% of cases) that appear in diabetic patients (usually on the foot and toes) as a result of specific lesions of microcirculation and nerve conduction. The remaining 2% of cases of trophic ulcers have a variety of etiologies: hypertensive (Martorell syndrome), infectious (syphilitic, tubercular, leprosy), occur in vasculitis, some metabolic syndromes, etc.

Regardless of the causes that caused the trophic ulcer, its treatment is a long process (sometimes, especially with frequent relapses, and lifelong), in which surgical methods, and physiotherapy, and, of course, various drugs, both local and and general action.

How to treat?
Treatment of the ulcer itself will be effective only if the cause that caused the trophism of the skin is eliminated simultaneously - without this, even if local treatment is successful and the ulcer is completely closed, relapses, the appearance of new ulcers on other skin areas, etc. are possible. In most cases, the direct cause is a violation of microcirculation, so in the complex therapy of trophic ulcers it is necessary to use agents that improve the rheological properties of the blood, increase the tone of the vessels (phlebotonics), prevent the formation of thrombi (fibrinolytics) and improve cell nutrition. Depending on the specific indications and contraindications, the patient can be assigned heparin and its derivatives, spasmolytics (drotaverin, nicotinic acid, papaverine), acetylsalicylic acid (Aspirin) and other drugs. One of the means widely used for the treatment and prevention of trophic ulcers of various etiologies is pentoxifylline, which has a complex effect: mild fibrinolytic, pronounced venotonic, lymphodrene; In addition, it positively affects the rheological characteristics of the blood. In some cases, pentoxifylline is prescribed together with prostaglandin E1 preparations, which promote the enhancement of capillary blood flow and prevent thrombogenesis. To improve cellular nutrition and respiration, Actovegin is used in clinical practice, which significantly increases oxygen consumption in cells, contains a significant amount of nutrients and microelements, and accelerates the processes of metabolism and, consequently, healing.

An important component of the complex treatment of trophic ulcers is the use of broad-spectrum antibiotics and antiseptic agents. Antibiotics are used not only for ulcers of infectious etiology, but also with such a frequent complication as the inflammation of the tissues surrounding the ulcer: in many cases they are caused by the drift of various microorganisms - both bacteria and fungi, therefore, if necessary, antimycotic preparations may be prescribed. To prevent infection of ulcers, regular antiseptic treatment and the application of aseptic coatings are required.

The problem of treatment of trophic ulcers is one of the most difficult in their treatment, since for the successful treatment it is necessary to remove both necrotic tissues and exudate and fibrin film (which along with the dead tissue can serve as a substrate for the development of microorganisms), and at the same time it is necessary to preserve as much as possible connective tissue components responsible for regeneration. To do this, use local remedies (mainly ointments) containing various proteolytic enzymes, for example collagenase (as part of the Iruksol ointment, etc.), selectively cleaving collagen at the border of dead and living tissues. This selectivity is due to the fact that the collagen of normal tissues is protected by mucopolysaccharides, which are absent on necrotic sites. Other collagenolytic enzymes are also used - for example, ultralizin or terrylitin, usually in complex preparations, which also contain antiseptics and sorbents. After the ulcer is cleared (both medically and by surgical methods), local anti-inflammatory, analgesic and wound-healing agents are used.

Modernity and prospects
Recently, more and more often local remedies are used not only in the form of traditional ointments, pastes, gels, etc., but also in the form of various wound coverings (bandages, films, patches, sponges, etc.) that provide a complex effect for a combination of the properties of the carrier material and various substances either impregnating the base material or included in its composition. Such coatings provide aseptic coverage of the ulcer and an optimum level of temperature and humidity of the healing surface, promote the elimination of toxins, the rejection of dead tissue (when proteolytic enzymes are included), drain excess exudate, and the like. Depending on the condition of the ulcer, the presence of pus, exudate, signs of inflammation, etc. various types of treatment coatings can be chosen. Unlike traditional bandages (paste impregnated with pastes, etc.), modern coatings do not dry up on the wound surface, therefore they are replaced without pain, irritation and trauma to the healing surface. In addition, the use of such products with different properties at different stages of treatment makes it possible to create an optimal environment for regeneration: recently specialists are inclined to believe that trophic ulcers should heal in a moist environment, which not only helps cicatrize the ulcer, but also allows the full restoration of tissues with proliferation and differentiation of cells, the formation of new microcapillaries, etc.

A promising area in the therapy of trophic ulcers is the use of biologics containing certain growth factors that selectively affect specific components of connective tissue. In addition, work is underway to create new-generation drugs based on specially grown cell cultures - however, while most of these drugs are too expensive for mass production, it is not always convenient to use and is used primarily in clinical experiments.

Diabetic foot

The diabetic foot syndrome is a complex of pathological changes in the peripheral nervous system, arterial and microcirculatory bed, which directly threaten ulcerative necrotic processes and foot gangrene in diabetic patients.

The syndrome of diabetic foot occurs in 4-10% of patients with diabetes mellitus. Mortality in elderly and senile patients with purulent-necrotic complications and gangrene of the extremities in diabetes mellitus reaches 20%. The factors of ulcerative-necrotic and purulent complications of feet are:

• the presence of neuropathy and angiopathy;
• deformities and swelling of the foot;
• skin condition - dryness, atrophy, turgor, cracks, hyperemia;
• ulcerative-necrotic complications in the anamnesis;
• diabetic retinopathy and nephropathy;
• elderly age;
• lonely residence of the patient;
• overweight;
• smoking and alcohol abuse;
• the presence of concomitant pathology, its severity and relationship with underlying pathology.

Prevention of complications of diabetic foot suggests:
- compensation for diabetes mellitus;
- early detection of patients with an increased risk of developing a diabetic foot syndrome;
- the risk rises with age and duration of the disease;
- inspections by a specialist for urgent measures;
- training of patients with the rules of foot care;
- examination by the dermatologist of the skin of the lower extremities of the patient with diabetes mellitus in order to detect mycosis at least once a year;
- Improve skin trophism and protect the skin barrier from external influences.

Fixed assets

Angioprotectors and correctors of microcirculation: Trental 400, Actovegin, Memoplant, Ginkoum, Doxilek, Calcium dobezilate tablets 250 mg, Complenamine, xanthinal nicotinate, Xanthinal nicotinate injection 15%, Agapurin, Agapurin 600 retard, Agapurin retard, Agapurin SR, Vazonite, Pentamon , pentoxifylline, Radomin, Trenpental, Trental, Troxerutin Lechiva, Dicynon, Angiovit, Solcoseryl, and others.

Antiaggregants: Ralofect, Raloect 300 N, etc.

Anticoagulants: Piyavit, Wessel Douay F, et al.

Carbapenems: Invanz et al.

Quinolones / fluoroquinolones: Avelox, Heinemox, Ciprolet A, Cyphran ST, etc.

Cephalosporins: Zeftera and others.

Hypoglycemic synthetic and other agents: Reclid, et al.

Calcium channel blockers: Cynedyl, cinnarizine, Cinnasan, and others.

n-anticholinergics: Midokalm, Midokalm-Richter, and others.

Serotonergic drugs: Serotonin, Serotonin adipate, etc.
Additional resources

Alpha-blockers: Redergin, Nicergolin, etc.

Antioxidants: Vitamin E, ascorbic acid, Mexidol and others.

Antiseptics and disinfectants: Betadin et al.

Dermatotropona funds: Balsamed intensiv balm for intensive daily care for dry sensitive skin of feet, Balsamed balm for daily care for sensitive skin of feet, Milgamma cream for foot care, Flexitol balm for foot care, etc.

Substitutes of plasma and other components of blood: Infukol GEK et al.

Immunomodulators: Derinat, Erbisol, Polyoxidonium, etc.

Correctors of cerebral circulation disorders: Cinnarizin Sopharma et al.

Enzymes and antiferments: Izodibut et al.

Ladasten - fast and safe treatment of asthenia

The saturation of modern life often takes away almost all the strength from people. Up to 40% of patients turn to general practitioners with complaints about the state of general frustration, emptiness, a sense of chronic fatigue. Such conditions are manifestations of asthenic syndrome, which is not always amenable to effective correction with the help of the usual methods: rest, playing sports, taking vitamins and nootropics. For a long time there was no available specific asthenia therapy. And only recently appeared the first anti-asthenic drug Ladasten.

- Why did you start developing a drug against asthenia?

"We have been working on the creation of a whole new group of psychotropic drugs for a long time. Back in the 1980s, it became clear to us that the existing tranquilizers of the benzodiazepine series have their limitations for use, and existing psychostimulants are practically banned. There are numerous immunostimulating agents, but they do not have other properties. Therefore, we are developing new medicines, with new mechanisms of action to bypass all the negative aspects that existing drugs have. And we have achieved some success. Ladasten (Bromantane), developed in our institute, does not have the negative effects of psychostimulants and tranquilizers and at the same time has high anti-asthenic activity.

- What is the drug Ladasten?
- Ladasten is a derivative of adamantane, which was invented in our institute long enough - back in the 70s. The primary idea of this drug was in the creation of a drug that would have actoprotective action. Actoprotectors are substances that must provide increased performance in extreme conditions. For the first time this preparation was synthesized under the guidance of prof. B.M. Pyatin, his further study was conducted by prof. I.S. Morozov. It was shown that this drug (then it was called bromantane) possesses psycho-stimulating and immunostimulating properties. Therefore, he immediately began to study in various pharmacological experiments. And when he was considered as a psychostimulant and compared with sidnocarb (a typical representative of this group of drugs), it turned out that Ladasten is much inferior to sindocarb in general stimulating properties, so further work with this drug was discontinued.

The drug received a new life when we began to study its psycho-stimulating properties from the pharmacogenetic positions. In the 1980s, we developed a model that allowed the most standardized inbred mice to see genetic differences in their reactions to emotional stress (for mice, such a stress is, for example, the transition from darkness to a brightly lit area). It turned out that one group of mice responds very well to standard psychostimulants (for example, amphetamine and sydnocarb), to which another group of animals does not respond. And on bromontane (Ladasten), the stimulation of behavior was answered by both groups of animals. This fact was difficult enough to explain. But we began to study this problem and realized that out of stress, stimulation only occurs in those animals that respond to traditional psychostimulants, and in those animals that do not respond, stimulation does not occur without stress. This led us to the unequivocal conclusion that the stimulation of the behavior of Ladasten is carried out in two ways - in addition to a mild psycho-stimulating action, this drug has an anxiolytic (anti-anxiety) effect, which prevents the reaction of fear. It was very interesting, because we got the world's first compound with psycho-stimulating and anti-anxiety action. Immunostimulating properties of the drug were also shown earlier.

- Why does Ladasten show such unique properties?
- We conducted very serious biochemical and neurochemical studies. Even involved a French firm that conducts a full complex of receptor analysis. We could not find the receptor on which Ladasten acts. Therefore, we studied various intracellular processes and saw that the secondary system of signal molecules plays an important role in the effect of the drug. The next stage was pharmacogenomic research. We studied the influence of Ladesten on the expression of 1116 genes and found a change in the activity of 16 genes. All the detected genes are associated with the functioning of the cells of the nervous system. Among these 16 genes, two were identified, the change in activity of which completely explained the observed pharmacological effects. Thus, Ladasten increases the expression of the tyrosine hydroxylase gene. This is a key enzyme that provides synthesis of catecholamines. This means that Ladasten, by increasing the activity of the tyrosine hydroxylase gene, increases the amount of this enzyme, which leads to the synthesis of more dopamine. This very well explains his mild psycho-stimulating effect. If you enter a typical psychostimulant, then there is a powerful psycho-stimulating effect, and then a strong exhaustion. When using Ladasten, the psychostimulating effect is weaker, but there is no depletion. Typical psychostimulants affect the release of dopamine from the storage vesicles and interact with the reverse dopamine transporter in the synaptic cleft. And Ladasten increases the synthesis of mediators associated with stimulation of the psyche. Thus, we are talking about an entirely new mechanism of action.

Analysis of other genes showed that Ladasten reduces the expression of the GABA transporter gene. This leads to an increase in the GABA content in the synaptic cleft, which in turn explains the anxiolytic (anti-anxiety) effect of the drug, since GABA is the main inhibitory mediator of the central nervous system of man.

Thus, pharmacogenomic studies have shown that the pharmacological effects of the drug are very well explained by the observed changes in gene expression. Now there is a clear idea that Ladasten affects the level of regulation of the activity of the genome of nerve cells. Studies continue, and it has already been shown that Ladasten increases the expression of the tyrosine hydroxylase gene, causing demethylation of its promoter site, and a transcription factor determining this effect is also revealed.

Thus, there is a sufficient understanding of what changes in cells causes Ladasten. And this confirms our confidence that the world's first drug has been obtained, which simultaneously causes an anti-anxiety and psychostimulating effect. Obviously, such a preparation fully meets the tasks of treating asthenic conditions.

- What side effects are possible with Ladasten?
- This issue was studied very deeply. Evaluation of toxicological characteristics of Ladasten showed that the drug is low-toxic. It does not have a locally irritating, allergic, mutagenic, teratogenic effect. Ladasten does not have a negative effect on the generative functions of rats, the growth and development of their offspring. Also, there were no effects that could indicate the possibility of developing a pathological predilection for him. The pharmacokinetics of the drug is well studied, and the dosage regimen is determined by data on its half-elimination from the body.

In clinical trials, all adverse events had only "possible" or "probable" connection with Ladasten therapy, were not significantly expressed and not.