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I spent about four The highest levels of tooth decay are found Exposure to fluoride is among the most when it hurt and that would do the minimizing the risk of tooth decay generic toprol xl 100mg online. During in middle-income countries discount toprol xl 25 mg with visa, where sugar cost-effective measures to prevent tooth trick quality 100 mg toprol xl. Then one day, the pain got so So we started taking our son for this time, though, I developed the consumption is on the rise and health decay and improve oral health. Regular use acute that I started having a fever regular dental checkups and we habit of snacking and drinking soda. I rushed to the dentist who knowing that we are taking the right impact on my life. I decided to go consequences of untreated tooth decay, Universal access to primary oral healthcare told me that my tooth was in such preventive measures to keep our son back to work, only my employer said particularly for children, are negative Existing inequalities in disease burden can bad shape that I needed a root canal in good health. Luckily our health he wouldn’t take me because I had impacts on nutrition and growth, loss of only be reduced with universal access to treatment. I didn’t realize days in school and at work, reduced overall primary oral healthcare, covering at least could have been quickly cured ended so we can do what is necessary for this had become so visible, but my productivity and significant impacts on relief of pain, promotion of oral health and up costing me numerous working our son’s wellbeing and overall bad eating habits had caused a lot of quality of life and social interactions. This was a mistake I will devastated to learn I couldn’t Teacher, Vancouver, Canada, to address the global tooth decay burden, not make again. This was a wake-up call to Full integration of oral health into popula- demiological surveillance. Inadequate oral hygiene leads to The defence of the local immune Because of the shared risk factors and its accumulation of dental plaque containing system breaks down and the two-way relationship with some systemic harmful bacteria and bacterial products that inflammation process advances. However, the global attention from healthcare professionals, cells of the immune system counter these pocket formation, with loss of governments, and insurance and pharmaceuti- damaging effects and the inflammation supporting bone. For many patients, the affected teeth may become loose disease never progresses beyond this point and be lost. Specialized periodontal care is not generally Links with general health available; when it is, it is unaffordable for Products from inflammation around the tooth and the bacteria in dental plaque enter the bloodstream and may cause systemic many. Diseases with an impact on the immune system, such as diabetes, increase the risk of more serious forms of periodontal severity data on a global level are scarce. Periodontal disease is a major public health regular check-ups, are important elements problem that challenges health systems in prevention of periodontal disease. It largely goes unnoticed is a strong social gradient in the prevalence by patients until it reaches an advanced of periodontal disease, which requires inter- “I was scared of stage. Public awareness of the disease and ventions addressing the wider determinants what that meant: the importance of proper oral hygiene is of health. Could I Periodontal disease shares common risk dontal disease can be detected at early “I started smoking in my early 20s. In about 10 to university, I was meeting people and going my gums were swollen and often bleeding collaboration 15 percent of patients, common gingivitis out… I was enjoying life. Then, some of my A holistic approach to managing periodontal may progress to severe periodontal disease, husband to-be when I started working. My told me I had suffered major bone loss and stronger collaboration between oral health disease has progressed to the stage where pregnancy was a joyful time in my life, which had severe periodontal disease. As with all chronic was sadly shadowed by some complications tioners and other appropriate health profes- I was scared of what that meant: Would I lose diseases, effective lifelong self-care, together linked to my baby’s premature birth. Could I afford key to preventing disease progression and warning me already about smoking and the that require care. I address severe periodontitis are required: myself I would smoke less and quit Integrated disease surveillance wish I had taken my doctor’s advice to stop eventually, but never really managed to. Healthy living and prevention Integrating indicators for periodontal dis- smoking when it could have made a I was around 40 when I started noticing gaps difference. I wish I knew back then what I The promotion of a generally healthy life- ease, together with other oral diseases, into between my teeth. Chewing tobacco, often with oral cancer: regular use of pipes, cigars, waterpipes, as However, the male–female ratio has other carcinogenic substances in betel quid, 95% About 95% of all well as all forms of smokeless dropped from 6 to 1 in 1950 is a common cause in Asia, while human papil- oral cancers occur tobacco (snus, chewing to about 2 to 1 at present. Timely referral to multi-disciplinary treatment factor, particularly in high-income countries. Such is the most common cause of their premature approaches are unavailable in many low- death. Generally, death rates for oral cancer and middle-income countries, particularly exceed those of many other cancers; only in South Asia, where existing facilities are Patient testimonies half of all patients survive the first five years overwhelmed with new cases. Despite advances in diagnosis the cost of care is beyond the means of “Head and neck cancer can be caused by “It was a terrible shock. I mean, I just went and treatment, this number has not changed many patients and their families. In addition, the impacts alcohol, drug abuse, genes, environment and detection made all the difference. I’m one of Integrative policies to address risk factors, of oral cancer, even after treatment, result in stress. Incidence, survival rates and detection made Early detection improves treatment outcomes Early awareness is a key factor. Yet, contributes to public awareness, all the huge inequalities based on socioeconomic I’m one of the delays in referral persist, even in high-income better. While Inclusion of oral cancer care in universal American Actor and Producer, 2013 general population screening is not recom- health coverage, the strengthening of health mended, there is good evidence for its effec- systems and a comprehensive approach to tiveness for patients with risk factors such risk-factor reduction may help in addressing “Early as smoking or high alcohol consumption. Oral cancer requires specialist care in dedi- Capacities in oral pathology and histological cated centres providing advanced surgery, diagnosis need to be strengthened. It is characterized by rapidly progress- political priorities for the eradication of noma. Rights Council, which has urged member states technical support to eight countries in the African as well as resource mobilization. Support comprehensive measures disease of poverty that contribute to reducing and neglect. Survivors suffer lifelong disfigurement and are poverty, malnutrition and other often left unable to speak or eat due to massive environmental and behavioural tissue destruction. But it goes disease burden occurs in Burkina Faso, Mali, further still, as an issue that Niger, Nigeria, Senegal and Ethiopia, which transgresses the boundaries are collectively labelled ‘the noma belt of the of human rights and world’. If they survive, patients require costly and complex surgery and this is often “The eradication of unavailable. Informing population groups at noma needs concerted risk, especially mothers, about the disease is efforts to alleviate poverty, Ensure referral of patients with vital if early detection and prevention are to be promote improved nutrition of advanced noma to specialist care. Clefts occur either alone (70 ance in patients with cleft lip and/or palate is 2006 mouth, creating a percent) or as part of a syndrome, affecting Sub-Saharan possible and can avoid social stigma, but it 3. Other minor congenital dental Cleft surgery was recently included in the anomalies, such as hypodontia (missing teeth) list of cost-effective essential surgery services Southern Europe 10. Sarah Hodges, Latin America, 5 Ensure that primary prevention and essential surgery services for birth Paediatric Anaesthesiologist, 23. Improving road safety, and introduc- Comparison of Europe I received a cross check directly to and Rwanda the teeth … The team dentist looked at improving public trauma deaths worldwide. They include frac- ing helmets, facemasks and mouthguards are Europe 2014, Rwanda tures of the jaws and other facial bones, as important measures in reducing the frequency me then proceeded to place a tongue health policies and 2003 well as fractures, dislocations and loss of and severity of dental and craniofacial trauma. Risk factors include traffic and bicycle fall Violence and child abuse are important I started to wear a mouthguard violence, sports and accidents, falls, physical violence, contact sports accident causes of oral injuries and have serious, and would never get on the road safety.
Once the site has been identified cheap 100 mg toprol xl fast delivery, environmental investigation of common site outbreaks parallels that of common event outbreaks Dispersed Environmental investigation of dispersed outbreaks is necessarily preceded by identification of the site cheap toprol xl 25 mg on line. It may involve product tracebacks to identify the sites and the processes involved in contamination Community-wide Environmental investigation of community-wide outbreaks is rare toprol xl 50 mg fast delivery. In unusual circumstances, environmental investigation may involve traceback of vaccine supplies or investigation for breaches of the vaccine cold-chain Institutional Environmental investigation of institutional outbreaks is similar to common event outbreaks in that the site of transmission is known at the outset. Investigation should involve hazard identification and collection of environmental specimens 9. Step 1: Identify the objectives of the environmental investigation Environmental investigation is required for all common event outbreaks. Objectives of common event outbreak environmental investigation include: identifying forthcoming events in which the circumstances of the common event under investigation may recur (e. Step 2: Decide when an environmental investigation can begin The circumstances associated with common event outbreaks are usually self-evident when the outbreak is initially reported. The preliminary stage of environmental investigation, that is, collection of background information, can therefore start at an early stage in the overall outbreak investigation. Full environmental risk assessment is a resource-intensive process, and may need to be delayed until provisional results of the epidemiological investigation are available. General information Before making the first visit to the implicated environmental site, become familiar with the types of processes that are likely to be encountered, and the regulatory environment and standards for these processes. This may involve: determining which agency has the legislative authority to investigate. It may be appropriate to either hand this part of the investigation to them or to conduct a joint investigation e. Specific information Information on many different types of environmental sites is collected routinely as part of licensing and normal regulatory arrangements. As an exception, water testing reports are often of value in the investigation of outbreaks involving water contamination. Liaising with territorial authority environmental health officers or other officials responsible for regulating the implicated site may be necessary. Information from key individual(s) associated with the implicated event Before visiting the implicated site or premises associated with the event, try to identify and make contact with key individual(s) involved with the event. Establishing a good relationship with the person or people responsible for the event can expedite a fast and thorough investigation, and will encourage the adoption of control measures. During the initial discussion: present the basic details of the outbreak, frankly and openly. Clearly state that the source of the outbreak has not been identified at this stage (if this is the case), and explain that preliminary enquiries are necessary at an early stage to help guide the investigation do not present suspicions about the outbreak source, unless the epidemiological analysis is complete arrange a mutually acceptable time for the site visit identify whether there are any forthcoming events in which the circumstances of the common event under investigation may recur (i. Step 4: Conduct a site visit and inspection Site visits and inspections provide the interface between the investigation and control of an outbreak. Observations made during the site visit may reveal helpful clues about the outbreak source, address general hygiene and safety issues, and can directly lead to implementation of control measures regardless of the subsequent epidemiological findings. The site visit is likely to have maximum benefit if undertaken as soon as possible after identification of the suspect site. A prompt visit would try to identify, sample, cease or remove from sale any food that could be contaminated. Also this initial rapid visit may identify gross problems at the site which may be immediately controlled. A second visit may occur when more detailed information has been gathered and analysed An additional function of visiting premises potentially linked to an outbreak is to meet those involved face to face. This emphasises the importance of the investigation, and when carried out in a polite and professional manner, tends to enhance communication and co-operation. Key components of the site visit and investigation are inspection of the place, processes and people. Remember that while doing a site visit and investigation, more is missed by not looking than not knowing. Place Gain a general impression of the site and keep an open mind, as unforeseen factors relevant to the outbreak may become apparent. This ‘floors, walls and ceilings’ inspection is only useful insofar that it contributes to an assessment of risk, as contaminated food can emerge from a kitchen that appears hygienic. While examining the site, consider whether specimens of leftover material associated with the common event are available and can be collected for testing. Collect specimens immediately, but if there is a lot of speculation on causative factors such as the specific source, mode of transmission or aetiological agent, it may be best to store the specimens after collection and decide what to test later. Ideally, the combined results of the epidemiological, environmental and laboratory investigation will help to guide decisions about what to test. Be cautious about widespread testing of the environmental specimens collected, because routine environmental culturing usually leads to results that cannot be 55 interpreted. For example, many surfaces, areas or items will be contaminated by organisms that are not relevant to the outbreak or are part of the normal environment, and yet the return of a positive test may demand a response. Processes The initial site visit is an opportunity to broadly review all processes at the site. If multiple processes occur at the site, it may be too time-consuming to undertake a detailed risk assessment of them all at the initial stage. It is important to include aspects that tend to be overlooked, such as storage, distribution, instructions to consumers, product design and composition. The following ‘process sieve’ has been developed to help screen processes for further detailed review. The process sieve If the site is unusual or has not been previously encountered, systematically identify which processes may have a role in the sequence of events that led to the outbreak. This process sieve offers a simple framework for screening processes that will require closer examination using the points listed above. The following processes are likely to require close examination: processes developed to decontaminate raw materials (e. People If the outbreak pathogen could have been transmitted from a person, then it is very important to interview and screen potential human sources using the following steps: identify a list of all individuals who may have come into contact with the suspected outbreak source(s) interview each individual with a standard questionnaire. The questionnaire should cover issues such as the presence or absence of symptoms of the outbreak illness, recent medical care or hospitalisation, presence of illness among close household contacts, level of contact with the suspected source(s) and involvement in other paid or unpaid work (e. Further information on questionnaire design is contained in Appendix 2 collect specimens if appropriate. If the pathogen can be transmitted by asymptomatic carriers, then all individuals who have had contact with the suspected source(s) should be screened. Step 5: Full environmental risk assessment Full environmental risk assessment requires a reasonable level of knowledge about the technical aspects of the processes potentially linked to the outbreak. It is beyond the scope of this manual to provide detailed descriptions of environmental risk assessment procedures and standards for the wide range of industries and processes with outbreak-causing potential. Discuss the characteristics of the outbreak with a technical advisor to obtain the most appropriate reference material. For the water industry, this material should be held in public health risk management plans. If this is the case, it may be important to take measurements, such as temperature readings, directly from the process itself. Environmental investigation of dispersed outbreaks Some form of environmental investigation is likely to be required for dispersed outbreaks.
Although vitamin C can be metabolized to oxalate buy 25mg toprol xl otc, routine restric- tion of vitamin C to prevent stone formation appears unwarranted order toprol xl 100 mg without prescription. However discount toprol xl 50 mg with visa, it should be noted that vitamin C may increase the risk of stone formation in a subgroup of persons with a urinary tract infection caused by a particular organism. Urinary ascorbate, if present at a high concentration in association with Proteus mirabilis infection, appears to be locally degraded to oxalate, potentially leading to calcium oxalate dep- osition on infection stones. Herbs that have choleretic and chola- Chapter 44 / Stones—Cholelithiasis and Urolithiasis 431 gogic effects include barberry, Oregon grape, dandelion, and wild yam. On the other hand, chamomile, a spasmolytic, may theoretically ease gallbladder pain. A terpene mixture reminiscent of peppermint oil is reputed to dissolve gallstones. Results of animal studies suggest that beneficial effects caused by herb infusions on urolithiasis can be attributed to some disinfectant action, and tentatively, to the presence of saponins. Herbs believed to prevent and treat kidney stone formation are Verbena officinalis, Lithospermum officinale, Taraxacum officinale, Equisetum arvense, Arctostaphylos uva-ursi, Arctium lappa, and Silene saxifraga. Hirvonen T, Pietinen P, Virtanen M, et al: Nutrient intake and use of beverages and the risk of kidney stones among male smokers, Am J Epidemiol 150:187-94, 1999. Mills S, Bone K: Principles and practice of phytotherapy, Edinburgh, 2000, Churchill Livingstone. Devesa F, Ferrando J, Caldentey M, et al: Cholelithiasic disease and associated factors in a Spanish population, Dig Dis Sci 46:1424-36, 2001. Mendez-Sanchez N, Gonzalez V, Aguayo P, et al: Fish oil (n-3) polyunsaturated fatty acids beneficially affect biliary cholesterol nucleation time in obese women losing weight, J Nutr 131:2300-3, 2001. Rattan V, Sidhu H, Vaidyanathan S, et al: Effect of combined supplementation of magnesium oxide and pyridoxine in calcium-oxalate stone formers, Urol Res 22:161-5, 1994. Hokama S, Toma C, Jahana M, et al: Ascorbate conversion to oxalate in alkaline milieu and Proteus mirabilis culture, Mol Urol 4:321-8, 2000. Grases F, Melero G, Costa-Bauza A, et al: Urolithiasis and phytotherapy, Int Urol Nephrol 26:507-11, 1994. Indications for urine culture are relaps- ing or recurrent infection, suspected pyelonephritis, complicated infections, or an uncertain history coupled with a dipstick positive for nitrites and/or leukocytes. A popular natural approach to treating urinary tract infection is consumption of 800 mg (400 mg twice daily) of cranberries or 500 mL of undiluted cranberry juice mixed with apple or pear juice to taste. In addition to attempts to prevent adherence of bacteria to the bladder wall, a possible prophylactic approach is colonization of the vulvovaginal area with commensals. A crossover trial demonstrated that daily ingestion of 150 mL of yogurt enriched with live Lactobacillus acidophilus organisms increased colonization of the rectum and vagina by these bacteria and may have reduced episodes of bacterial vaginosis. However, an open, random- ized, controlled trial (over 1 year) of consumption of 50 mL of cranberry- lingonberry juice concentrate daily for 6 months or regular consumption of 100 mL of lactobacilli 5 days a week showed that cranberry juice, but not lactobacilli, seemed to reduce the recurrence of urinary tract infections. Infected urine may contain considerable amounts of nitrite as a result of bacterial nitrate reductase activity. In fact, detection of nitrite in urine is routinely used in the diagnosis of bacterial cystitis. Results of a lab- oratory study confirmed that nitrite-producing bacteria, such as E. However, the clinical relevance of urinary acidi- fication with ascorbic acid is doubtful, because 1. Cranberry tablets are available, but results of a small trial suggest that they may increase the risk of urinary stones. Other herbs that may be useful include goldenseal, a urinary antiseptic, and dandelion, an herbal diuretic. Drinking one cup of hot nettle tea made from a teaspoon of the dried herb may be helpful. Reid G: Potential preventive strategies and therapies in urinary tract infection, World J Urol 17:359-63, 1999. Reid G, Hsiehl J, Potter P, et al: Cranberry juice consumption may reduce biofilms on uroepithelial cells: pilot study in spinal cord injured patients, Spinal Cord 39:26-30, 2001. Shalev E, Battino S, Weiner E, et al: Ingestion of yogurt containing Lactobacillus acidophilus compared with pasteurized yogurt as prophylaxis for recurrent candidal vaginitis and bacterial vaginosis, Arch Fam Med 5:593-6, 1996. Mills S, Bone K: Principles and practice of phytotherapy, Edinburgh, 2000, Churchill Livingstone. Diefendorf D, Healey J, Kalyn W, editors: The healing power of vitamins, minerals and herbs, Surry Hills, Australia, 2000, Readers Digest. A loss of vas- cular integrity is associated with the pathogenesis of both hemorrhoids and varicose veins. Any prolonged obstruction to venous draining is accompanied by varying degrees of venous insufficiency. Hemorrhoids, varices of the superior hemorrhoidal vein that drains the anorectal area, present as bleeding on defecation. Blood may splatter the bedpan or be streaked on the toilet paper or the stool’s surface. Depending on the magnitude of the hemorrhoid, bleeding may be associated with varying degrees of protrusion of the anal mucosa. The larger and more persistent the prolapse, the greater is the likelihood of a mucoid discharge and anal pruritus. Although often asymptomatic, varicose veins may present as a dull, aching heaviness exacerbated by standing and improved by walking or elevating the leg. Because superficial veins are poorly sup- ported, they tend to become tortuous if exposed to high venous back pres- sure, as may occur with valvular incompetence or deep vein thrombosis. Deep vein thrombosis is an important cause of impaired drainage that results in venous insufficiency. Chronic venous insufficiency is most com- monly encountered in the lower limbs as a result of thrombosis of the deep veins of the lower limbs. The mildest form of venous insufficiency is mini- mal edema after prolonged standing. More clinically relevant is chronic venous insufficiency, which presents as progressive leg edema, pruritic atrophic skin, a cyanotic limb, and chronic recurrent ulceration. Excess pressure on a normal or weakened 437 438 Part Two / Disease Management vessel wall predisposes the vessel to tortuosity. The likelihood of venous tortuosity is increased by pressure such as that which occurs with venous valvular incompetence or straining on defecation as in constipation. Impaired blood flow may result from partial or complete occlusion of the vessel lumen, most often caused by thrombosis. Preventing deep vein thrombosis reduces the risk of both varicose veins and venous insufficiency. The risk of thrombosis is increased by stasis, damage to the intima of the vessel wall, or increased blood coagulability. The aims of intervention are to prevent external occlusive pressure on the vessel wall, to improve venous tone, and to prevent blood coagulation. Good bowel habits are fundamental to decreasing the risk of hemorrhoids, constipation, and straining on defecation.
There are many different methods tions leading to decreased receptor activity due to to prevent the progressive loss of vision toprol xl 100mg lowest price. Most of the known by up to 10 years; ñ docosahexaenoic acid supple- rhodopsin mutations are constitutively active mentation cheap toprol xl 25mg mastercard, which belongs to the group of ω-3 acids generic toprol xl 25 mg with visa. As a result, there ñ oxygen therapy ñ in normal conditions, retinal is a dysfunction of rods, resulting in impairment of photoreceptors have high oxygen consumption. Analyzing the process of Pro23Leu, Gln28His, Glu113Gln and Lys296Glu photoreceptor cell death, it was found that it was (4). As the disease causes a reduction in its degeneration in examined progresses, there is a total loss of the peripheral mice. Properties and action of nilvadipine prove to G protein-coupled receptors: abnormalities in signal transmission. Nilvadipine is a Based on both studies, we can say that desensitiza- hydrophobic drug, making it easier to go to the cen- tion is one of the key processes determining the tral nervous system and retina. An additional advantage of nilvadipine is (adrenaline and noradrenaline) regulate the activity the highest antioxidant potential among calcium of the sympathetic nervous system. Polymorphisms caused by mutations in the gene Studies concerning the effects of calcium channel promoter can cause changes in the expression of inhibitors on apoptosis are still conducted (19). Treatment consists in placing in the ple, β1 receptor variant (arginine at 389 is converted conjunctival sac drops of a mixture of insulin with to glycine) and α2 receptor variant (asparagine at growth factor, which helps in the recovery of Muller 251 is converted to lysine). It is a glial type of cells in the retina, that pro- receptor dysfunction in the intracellular signaling tect photoreceptor cells against excess of glutamate process and as a result occurs an increase in the and free radicals. Depending on the rods mainly, which come from the same progenitor type of polymorphism, a variant can have a major cells as the Muller cells. Research on this method of impact on the course of the disease, or only a poten- treatment offers hope to achieve a simple treatment tial risk of its development. It is a rare to medicines used in the treatment of a specific dis- disease involving disturbances of vision at dark, at ease (4). The first (β1 receptor) is arestin, and in result, there is a lack of rhodopsin located mainly in the heart, where it influences the phosphorylation. In patients, who have this muta- pulse rate and myocardial contractility, and in the tion, receptor constantly activated by light, constant- kidneys, in which it directs the release of renin. As response to stimulation by rhodopsin regeneration takes more than two hours, endogenous ligands of the sympathetic nervous sys- after which the rods again reach their full sensitivity tem, the widening of blood vessels (vasodilation) to light. In other research, in ble and unstable coronary artery disease (angina vivo, there was no phosphorylation of rhodopsin. Such variant is often associated with ele- commonly used drugs as these used in the treatment vated level of immunoglobulin E in asthma (4). In of bronchial asthma (β2 agonists), and diseases of addition, those who had Arg16Gly polymorphism, the cardiovascular system (β1 antagonists) (22). The receptor with polymor- the β1-adrenergic receptor are the results of a sin- phism at position 16 of the peptide chain, under the gle amino acid replacement at positions 49 and 389. As in the case of Gly16Arg, this receptor is the C-terminus of the peptide chain, arginine is sub- also down regulated (14). In studies carried on hamsters phism results from threonine substitution for fibroblasts, there has been shown that substitution of isoleucine at 164 position. Despite the fact, that it the glycine at position 49 in the receptor resulted in occurs rarely, it has a significant impact on the func- a decrease in the number and density of receptors on tion of the receptor. Binding to the G protein and the the cell surface as a result of its down regulation. It has Various polymorphisms within the β1 receptor also been shown that it causes disturbances in the may affect the bodyís response to medications. The process of vasodilation, thus contributing to an difference in the individualís response in humans increase in blood pressure, the frequency of hyper- with a mutated form of this protein is particularly tension and other cardiovascular diseases. In the Arg389Gly intensifies response to drugs, which are group of study there were Danish men and women β1-adrenergic receptor agonists as well as to antago- of Caucasian origin. It was shown that treatment presence of Thr164Ile is associated with increased with dobutamine or adrenaline has better effect on blood pressure and the other above-mentioned function of the heart of people with Arg389Gly changes in the cardiovascular system in women polymorphism, who underwent coronary artery (23). Thr164Ile polymorphic variant may occur in bypass grafting, in relation to persons having a patients suffering from heart failure and affects Gly389Arg polymorphism. It turned out that in treatment of cardiac failure, for example, by increas- patients with a mutation Arg389Gly, a better ing the dose of the drug (4). On the mine their potential impact on the development of basis of this result, it was assumed that persons with the disease and is useful in predicting the response Arg389Gly polymorphism in the gene encoding the to medications used during treatment. As a gested that, in order to quicker obtain the favorable result of the above diseases, there is an insufficient therapeutic effects, administration of the higher dose blood flow and myocardial ischemia, and necrosis of such drugs to persons without polymorphism of the tissue. These mutations have been compensating ineffective myocardial work are: acti- observed in diseases such as hypertension, asthma, vation of the sympathetic nervous system, stimula- obesity, and certain immune disorders. At described, there is an increase in cardiac workload, G protein-coupled receptors: abnormalities in signal transmission. Activation of both types the next step, there are changes in the structure of of receptor (β1 and β2)causes stimulation of protein the myocardium. In addition, cascade is an increase of frequency, strength and there are risk factors that can facilitate the incidence speed of contraction of the heart muscle and of heart failure. They can be divided into physiolog- increase of the relaxation phase of the muscle fibers. The second group due to the fact, that its continuous stimulation caus- includes, among others, changes in the expression of es apoptosis of cardiomyocytes. In contrast, β2 genes encoding the receptors that can influence the receptor is considered to be cardioprotective. Polymorphic variants of β-adrenergic receptors and their influence on the pathogenesis of cardiovascular disease (22, 23). Receptor Polymorphism Signal change Clinical observations Gly49 Gly49 Ser49Gly ñ increase of the susceptibility ñ reduced risk of deepening of receptor on down regulation failure, heart transplantation or death Homozygotes Arg389 ñ better treatment effects of β-blockers Arg389 in the form of an increase ñ binds stronger Gs protein in left ventricular ejection β1 Gly389Arg ñ receptor more sensitive fraction than Gly389, to stimulation with agonist an increase the risk and antagonist of arrhythmia. In extreme cases, it may lead to the dis- brane; c) reduced constitutive activity of the recep- appearance of up to 50% of β1 receptors. After the interaction of continuous stimulation of β2 receptors, there is not the receptor with α-melanocortin, there is no answer its down regulation but there is an increase of the or it is limited and this could happened because of inhibitory Gi protein concentration. In consequence, the reduced receptor affinity for agonists or weak there is a weakening of the response to continuous signal transduction. Disorders classified in the sec- stimulation of the sympathetic nervous system (22). It was demonstrated that 80% of children More and more people around the world suffer with severe obesity have showed a partial or com- from the problem of obesity. In ilization disease are lifestyle changes, diet and the last group of receptor disorders, there are muta- genetic factors. Significant influence on the devel- tions that result in a loss of constitutive activity of opment of obesity has a mutation in the gene encod- the receptor.
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