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However buy lasix 100mg visa ocular hypertension, in the given example buy lasix toronto arteria coronaria izquierda, this compound undergoes dibromination by molecular bromine buy generic lasix 40 mg on line hypertension young women, giving 2,4-dibromo-derivative of dihydrocortisone 27. Dehydrobromination with 3,5-lutidine, followed by subsequent hydrolysis of the acetyl group using potassium bicar- bonate gives the desired prednisone (27. Prednisone is also synthesized by microbiological dehydrogenation of cortisone [16,17]. Structurally, prednisolone differs from prednisone in that the keto-group at C11 of prednisone is replaced by a hydroxyl group. Prednisolone is synthesized either by microbio- logical dehydrogenation of C1–C2 bond in hydrocortisone [16–19], or from 21-acetoxy- 11β,17α-dihydroxy-5α-pregnan-3,20-dione, which undergoes dibromination by molecular bromine in acetic acid at positions C2 and C4, and then the resulting dibromide 27. It raises glucose levels in the blood, increases potassium secretion, and reduces sodium secretion from the organism. Prednisolone is used for the same indications as all corticosteroids: rheumatism, poly- arthritis, bronchial asthma, neurodermatitis, and eczema. Synonyms of this drug are anti- solon, decortin, cortolon, precortilon, and many others. This seemingly simple difference in struc- ture requires a different approach to synthesis. Next, the resulting epoxide is reacted with methylmagnesium bromide, and sub- sequent removal of the ketal protection by hydrogen reduction gives the 5-hydroxy-6-methyl derivative of dihydrocortisone 27. The resulting β-hydroxyketone is dehydrated using an alkaline, and then the resulting 6α-methylcortisone (27. The distinc- tive characteristic of dexamethasone is the presence of a fluorine atom at C9 of the steroid ring. Dexamethasone is synthesized in a multistage process from 3α-acetoxy-16-pregnen- 11,20-dione, which is reacted with methylmagnesium bromide in the presence of lithium bromide to give 3α-hydroxy-16α-methylpregnan-11,20-dione (27. This is done by a reaction with acetic anhydride in the presence of p-toluenesulfonic acid, forming the 3-acetoxy-17-enolacetate 27. Addition of another hydroxyl group at C21 is accomplished by subsequent bromina- tion of a methyl group with molecular bromine, replacing the bromine atom with iodine, and reacting iodide with potassium acetate, which forms the corresponding acetoxyketone 27. Dehydrogenation of this compound is accomplished using semi- carbazide, which results in the formation of an unsaturated triketone 27. In order to avoid formation of semicarbazones at the keto-groups at C3 and C20, the final product is treated with pyruvic acid. Semicarbazones are then specially formed at the keto-groups of C3 and C20, and the keto-group at C11 that does not take part in semicarbazone formation is reduced to hydroxyl group using sodium borohydride. After removing the protective semi- carbzone groups, 21-O-acetoxy-16β-methylhydrocortisone (27. Reacting this with hydrofluoric acid results in an opening of the epoxide ring, during which the fluorohydrin 27. Finally, microbiological dehydrogenation of this compound at C1–C2 and simultaneous deacetylation gives dexamethasone (27. It is used for circulatory collapse—shock during or after surgical operations, trauma, blood loss, myocardial infarction, and burns. It is also used in severe infections—toxemia, vascular collapse in meningococcosis, septicemia, diphtheria, typhoid fever, and peritoni- tis. It is used in severe allergic conditions—asthmatic status, laryngeal edema, severe ana- phylactic reactions to medicinal drugs, and pyrogenic reactions. Betamethasone: Betamethasone is 9α-fluoro-16β-methyl-11 β,17,21-trihydroxypregna- 1,4-dien-3,20-dione, or simply 9α-fluoro-16β-methylprednisolone (27. As seen from the chemical name of the drug, betamethasone only differs from dexamethasone in the ori- entation of the methyl group at C16. The proposed method of synthesis differs from the other method in a number of details and successive reactions besides the first stage, in particular concerning the addition of the methyl group at C16 of the steroid ring. Betamethasone, like dexamethasone, is synthesized from 3α-acetoxy-16-pregnen-11,20-dione; however, the methyl group at C16 of the steroid ring is not reacted with methylbromide, but rather is reacted with diazomethane followed by hydrogenation of the double bond between carbon atoms C16–C17 of the steroid ring using a palladium on carbon catalyst, which results in the corresponding β-orientation of the introduced methyl group . In the first stage, both carbonyl groups of this compound undergo ketalization by ethylene glycol. Acetylating the hydroxyl group once again with acetic anhydride gives a triene 27. The secondary hydroxyl group at C16 of this product undergoes acetylation by acetic anhydride in pyridine, which forms the diacetate 27. Treating the product with N-bromoacetamide in chloric acid gives a bromohydrin (27. Opening of the epoxide ring, using hydrofluoric acid, gives the corresponding 9-fluoro-11-hydroxy derivative 27. Upon microbiological dehydrogenation, the C1–C2 bond is oxidized to a double bond, forming triamcinolone acetate (27. Corticosteroids Triamcinolone is similar to dexamethasone in terms of pharmacological action, and it is better tolerated in some cases. The main endogenic mineralocorticoid is aldosterone, which is not used in clinical med- icine, however. Unlike glucocorticoids, mineralocorticoids have an insignificant effect on carbohydrate volume. They are used for chronic adrenal insufficiency, as well as for raising tonicity and work capacity of muscles. The correlation between chemical structure and action of mineralocorticoids is extremely complex; however, a number of partial conclusions can be synthesized. The necessity of either a simulta- neous presence of acidic functions at C11 and C18, or the necessity of simultaneous absence of acidic functions at C11 and C17 in the structure of the pregnane system is also apparent. Fluorination at C9α-position increases the mineralocorticoid activity of both C11-hydroxy (hydrocortisone) and C11-deoxy (deoxycorticosterone) compounds. Alkaline hydrolysis of the acetyl group of this compound leads to the desired aldosterone (27. Reacting this with isopropenylacetate in the presence of p-toluenesulfonic acid gives the enolacetate 27. Treating the resulting enolacetate with iodosuccinimide, which reacts exclusively with the enolacetate double bond, an iodoketone is formed, which is reacted with potassium acetate to form the acetate 27. The double bond at C16–C17 is reduced by hydrogen using a palladium on carbon catalyst, forming the product 27. Oxidizing this product with aluminum, isopropylate in the presence of cyclohexanone gives desoxycorticosterone acetate (27. Corticosteroids Desoxycorticosterone causes an increase in reabsorption of sodium ions and excretion of potassium ions from the renal tubules, which leads to increased tissue hydrophilicity. It is used for an insufficiency of function of the adre- nal cortex, myasthenia, asthenia, adynamia, and overall muscle weakness. In the first stage of synthesis, dehydration of the hydrocortisone molecules is accomplished using phosphorous chloride in pyridine, which forms a product with a double bond at C9–C11 27. The resulting double bond is synthesized into an epoxide by an initial transformation to a bro- mohydrine using N-bromoacetamide and subsequent dehydrobromination using sodium acetate, which forms 21-O-acetoxy-9d-11β-epoxy-17α-hydroxy-4-pregnen-3,20-dione (27. As described above, the epoxide ring is opened by hydrofluoric acid, which results in the formation of the 21-O-acetate of fludrocortisone 27. Hydrolysis of the acetyl group of this compound using potassium acetate gives fludrocortisone (27.
Tazarotene buy generic lasix 100mg line blood pressure xls, another recently studied retinoid 100mg lasix sale blood pressure readings, has been shown to be effec- tive in psoriasis and acne will likely be effective in photoaging (27) discount lasix express arrhythmia uti. Retinol, the prototypic retinoid, is the alcohol of retinoic acid and has been shown to be somewhat active in animal models of photodamage. Data to substantiate this cosmetic claim (not the same as pharma- ceutical efﬁcacy substantiation) are not included in the advertisements. Hormones and Vitamins As many hormone and vitamin deﬁciencies adversely affect the skin and as many of the skin functions and structures have been shown to be affected by hormonal Photoaging 27 or vitamin treatment, it is surprising that there has not recently been more quality research in the area of hormonal and vitamin effects or attention focused on the therapeutic use of androgen, thyroid, or growth hormones topically applied in photoaging. Androgens Androgens play a major role in skin physiology and are especially important in regulation of hair growth and sebum secretion. Less is known about their anabolic capabilities in skin but one would conclude that they should produce beneﬁcial effects on aging and photoaging skin although conclusive proof is presently lacking. Estrogens A modest literature does exist, however, supporting the utility of estrogens in reversing at least some of the sequelae of skin aging. Clinically, improvement of elasticity, ﬁrmness, skin moisture, vascularization, and wrinkling were noted. A randomized, double-blind study of 54 women aged 52 to 70 years with moderate-to-severe facial cutaneous aging compared treatment with either 1 g Premarin cream (0. A statistically signiﬁcant difference in skin thickness measured by B-scan ultrasonic echography was demonstrated at week 24 in the Premarin-treated group. Clinically, signiﬁcant improve- 28 Cunningham ments in roughness, laxity, and mottled hyperpigmentation were noted by the investigator, but no differences from baseline or between the two groups were noted in subjects’ self-evaluations of overall facial appearance or wrinkling of the crow’s feet area. Although pre- and posthormone determinations were not obtained in this study, a signiﬁcant difference from baseline in the vaginal matu- ration index was noted in the Premarin-treated group, indicating probable sys- temic effect. Both groups demonstrated signiﬁcant decreases of wrinkle depth measured by optical proﬁlimetry as well as clinical improvement in elasticity and ﬁrmness of the skin. No evidence of systemic hormonal effect was noted except for an increase in prolactin levels. Vitamins Vitamin D Many vitamin D analogues have demonstrated effects on epidermal cells and ﬁbroblasts and they have achieved quick acceptance in treatment of psoriasis. As some of their properties resemble those of retinoids, modulation of epidermal differentiation is possible and should be investigated in photoaging. Vitamin C As with claims for retinol in cosmetic products, the claims made for topical vita- min C are still more cosmetic than documented pharmaceutical. Vitamin E Vitamin E is an antioxidant in many systems and has been proposed, studied, and promoted for a large number of diverse systemic and skin conditions (33). On a theoretical basis, the concept of utility of the antioxidant effect of vitamin E is appealing, but, although the literature is voluminous, it is not completely convincing of a pharmaceutical effect in most conditions including skin disease, photoprotection, or photoaging. A 10-day study by the same investigators claimed Photoaging 29 enhanced skin smoothness with topical vitamin E. In a pilot study, a 25% increase in skin thickness was noted, comprised of both epidermal and dermal contributions. Increased acid mu- copolysaccharides, improvement in elastic ﬁber quality, and increase in collagen density were also noted (35). A 22-week double-blind study conﬁrmed utility of both 8% glycolic and 8% lactic acid in treatment of photodamaged skin in overall appearance and in speciﬁc parameters of mottled pigmentation, sallowness, and roughness (36). The beta-hydroxy acid, salicylic acid, has been studied for its effects on photodamage in a large number of women during a home-use trial versus a propri- etary glycolic acid cream and was observed to be superior on global improvement of appearance (37). Hydroquinones These agents, as weak depigmenting agents, may occasionally be of some utility in treatment of the epidermal pigmentary irregularities associated with pho- toaging. Higher concentrations, better delivery systems, and combination with other active products may enhance their utility in treatment of pigmentary abnor- malities related to photoaging. Minerals The legends surrounding Cleopatra, the ancient Queen of Eygypt, are numerous. Frequently referenced in advertising of cosmetics, she is said to have claimed the rights to the Dead Sea’s mineral ingredients and, most naturally, these ingredi- ents have claimed numerous cosmetic properties (39). Some contain a high concentration of divalent cations, magnesium, and calcium and a lower concentration of mono- 30 Cunningham valent cations sodium and potassium as well as miscellaneous other cations and anions. Zinc and selenium have been frequently studied in dermatological condi- tions, most often inconclusively for true pharmacological effect, but these and other minerals unquestionably play major roles in normal physiology of the mam- malian organism. Most notably, their vital roles as cofactors in enzymatic pro- cesses means that they cannot be completely dismissed in spite of sometimes extravagant marketing claims. Much conﬁrmatory work is needed to fully sub- stantiate cosmeceutically oriented claims of skin penetration, restoration of mois- ture because of hydroscopic characteristics, and, importantly, actual participation as cofactors in enzymatic regulation activities in the metabolism of healthy or photoaged skin. Hyaluronic Acid Hyaluronic acid plays a key role in both epidermis and especially dermis. Its water-holding properties are well established and, more recently, its involvement in control of cell growth, membrane receptor function, and adhesion have been demonstrated. A progressive reduction in electron-dense granules of hyaluronic acid has been observed with increasing age (40). Furthermore, application of topical tretinoin to photoaged skin has been demonstrated to increase both epidermal and dermal hyaluronic acid theoretically increasing water-holding capacity and possibly facilitating other intercellular transports (42). Natural Cartilage Polysaccharides Vivida, an oral formulation containing 500 mg/day of puriﬁed natural polysac- charides from cartilage of marine ﬁsh was compared with a placebo in a study of 30 women aged 40 to 50 years with sun-damaged skin (44). No changes were noted in the placebo group, but in the Vivida group, after 90 days, the epidermal thickness increased from 0. Imedeen, a different commercial preparation of natural cartilage polysac- charides containing 380 mg of active substance was compared to Vivida 500 mg/ Photoaging 31 day in a second study of 30 women aged 40 to 60 years (45). Conﬁrmation of these results in larger, controlled multicenter studies, as well as explanation of how an oral preparation of polysaccharides would survive the digestive system and reach the systemic circulation and, therefore, the skin, is needed. The substances and products described above are at least partially clinically substantiated as having a cosmeceutical action in photoaging and in many cases have a theoretical basis for action. A host of additional putative agents has been described with new additions monthly. A recent review discusses potentially skin-active naturally occurring botanicals including familiar substances such as chamomile, ginseng, hops, etc. Substantiation of effect in photoaging is not available, but in view of the long-standing folklore surrounding some, an open mind and meticulous investigation are prudent. Minoxidil Topically applied minoxidil provides another example of modest pharmacologi- cal action with cosmeceutical impact and is modestly effective in treatment of androgenetic alopecia by conversion of some telogen follicles to anagen possibly via K-channel mechanisms. It would be interesting to study this class of molecule in photoaging to see if the ‘‘resting’’ aged epidermis and dermis could be simi- larly stimulated to a more active state. Last, although it is not the speciﬁc purvue of cosmeceuticals, multiple inter- ventions from conventional surgery to laser techniques have been detailed to affect photoaging. One new device has recently been described which may fore- tell the future treatment of many diseases and conditions of the skin. A depth- targeted gene delivery and expression in the skin utilizing pulsed electric ﬁelds has been discussed in the context of skin aging (47). It has become increasingly clear that manipulation of gene action by various techniques, be they indirect such as hormonal, receptor-mediated up- or downregulation of genetic control, or direct intervention by substitution of new gene material into the cell nucleus, are feasible and productive in regulation of various skin dysfunctions.
Tip #3: Get It Out In Chapter 5 lasix 100mg otc blood pressure monitor reviews, I also talked about how destructive repressed emotions are lasix 100mg for sale blood pressure normal heart rate high. So no matter what kind of emotional stress you’re under purchase lasix online pills blood pressure medication recreational, it’s important to get it out—in a healthy way. For the more severe cases of emotional trauma, such as death, divorce, abandonment, and abuse, the techniques for managing everyday stress may not be enough. One advanced technique is to write down the pent-up emotions you’re feeling (the most common one is anger). Use a pen and notepad, your computer, or even a voice recorder to get your emotions out. Start with feeling words like “I’m angry about…,” “I wish…,” “I’m sorry for…,” “I feel…,” and other similar expressions to encourage emotional responses. Typically, these kinds of exercises help clear your head and release the pressure that emotions can create in the body. For serious traumas that may have occurred in the past but that were never resolved, it’s best to seek out the assistance of a licensed therapist. Even if you’re not sure such a trauma could be causing your back pain, if you’ve experienced something very difficult—a crime, childhood abandonment 141 The 7-Day Back Pain Cure Balance Your Emotional State of Mind 142 downsizing your lifestyle, and the bills that go with it, can or abuse, rape, or other type of violence—it’s paramount that provide instant stress relief. If you’ve In general, take a good look at your life—your job, your suppressed the emotions surrounding these events, you may surroundings, your schedule, your friends and family—and not be aware of the damage they’re causing. Whenever with a reputable therapist and see if you notice an possible, eliminate the draining factors. Some types of therapy you may want to consider are gestalt Tip #3: therapy, family constellation therapy, and hypnosis. Get It Out Tip #4: In Chapter 5, I also talked about how destructive repressed Manage the Stress You Do Have emotions are. So no matter what kind of emotional stress you’re under, it’s Stress is not all bad. So, after you’ve eliminated all the stress you can, you must For the more severe cases of emotional trauma, such as decide how to manage what remains. It releases your body’s natural feel-good endorphins, technique is to write down the pent-up emotions you’re gives you energy, relieves pain, burns calories (potentially feeling (the most common one is anger). There’s Use a pen and notepad, your computer, or even a voice really no end to the benefits of this powerful coping recorder to get your emotions out. First thing feel…,” and other similar expressions to encourage emotional in the morning, as a break at midday (a lunchtime walk can responses. Typically, these kinds of exercises help clear your do wonders), as a bridge between work and home life— head and release the pressure that emotions can create in the however it works best for you. For serious traumas that may have occurred in the past but Resist the impulse to say, “Well, I can exercise tomorrow. Take the appointments you make could be causing your back pain, if you’ve experienced with yourself just as seriously. Taking 10–20 minutes a day to be still, breathe deep, and center your thoughts quiets both the mind and the body, reducing all the stress-induced changes that are so bad for your health. Many meditation techniques really emphasize slow, deep breathing—which is great for getting more oxygen into your muscle cells, reducing the likelihood of trigger points. It’s also the exact opposite of the fast and shallow breathing pattern we typically use when we’re stressed. This ancient form of stretching and exercising trains you to focus on the breath while moving your body into a myriad of poses that help you gain flexibility and strength. Many of my clients swear by yoga as a way to help them relax, reduce back pain, and sleep better. If you’re going through a particularly rough time and you can’t change the circumstances, you may need a more powerful form of stress relief, such as hypnosis. I’m not suggesting swinging pocket watches or dancing like a chicken—the sorts of things we see on television or in entertainment shows. The type of hypnosis I’m talking about is like a form of deep meditation that can relieve pain by reaching the depths of your unconscious mind. Maggie Philips, guides you through 10 exercises that help you learn to reverse the course of chronic pain. There are a myriad of ways to cope with stress and to process the difficult emotions in your life. What you must not do is ignore your feelings, muddle through them, or think you’re strong enough to just stuff them away. If you want to get rid of back pain, experiment with Taking 10–20 minutes a day to be still, breathe deep, and coping techniques, find the ones that work for you, and center your thoughts quiets both the mind and the body, implement them in your life. If you want to feel better, it’s reducing all the stress-induced changes that are so bad for imperative! Many meditation techniques really emphasize Here are some online resources you may want to explore: slow, deep breathing—which is great for getting more oxygen into your muscle cells, reducing the likelihood of trigger • www. Many of my clients swear by yoga as a way to help them relax, reduce back pain, and sleep better. If you’re going through a particularly rough time and you can’t change the circumstances, you may need a more powerful form of stress relief, such as hypnosis. I’m not suggesting swinging pocket watches or dancing like a chicken—the sorts of things we see on television or in entertainment shows. The type of hypnosis I’m talking about is like a form of deep meditation that can relieve pain by reaching the depths of your unconscious mind. Maggie Philips, guides you through 10 exercises that help you learn to reverse the course of chronic pain. There are a myriad of ways to cope with stress and to process the difficult emotions in your life. What you must not do is ignore your feelings, muddle through them, or think you’re strong enough to just stuff them away. But I do want to emphasize just how important your nutrition is to your ability to live without pain. When we drink more, we re-inflate those discs after they’ve been depleted throughout the day. Water helps eliminate toxins from the body and promotes more efficient kidney function. Flushing toxins out on a regular basis can help prevent trigger points from forming and reduce the severity of those already present in the muscle tissues. It fills the stomach, which can deter us from eating too much, and helps to keep our energy levels high. The “eight glasses a day” rule is a good general guideline, but remember, everyone is different. Everyone has a different weight, metabolism, and activity level, so you need to experiment with what’s right for you.
If it is self-administered discount lasix 40 mg fast delivery blood pressure jumps from low to high, you may want a queston on whether the person had help in answering the questonnaire effective lasix 40 mg pulse pressure waveform. Check each queston with the objectves of the study and use your list of variables as a guide for deciding how to phrase the queston in relaton to the data to be collected buy 100 mg lasix free shipping arteria iliaca communis. Draw dummy tables of desired data based on the questonnaire to ensure that all informaton required can be captured. Where possible, every queston should be designed to be answered, even if this is in a negatve way, e. Check content validity with experts in the area – verify that important areas are addressed appropriately. Pre-test the questonnaire on individuals who are similar to (but not part of) your study populaton to ensure that: a. Internal consistency: This is checking to see if questons asking the same thing get similar answers from the same person. Test-retest reliability: This is checking if the same person will answer the same way on repeated testng on diferent days. If possible, use or modify a pre-existng checklist (ask for permission to use and remember to acknowledge the source in your write-up). Check each item with the objectves of the study and use your list of variables as a guide for deciding on the areas of data to be collected. In a waitng tme study, the tme measured could be defned, from patent registraton to patent entering the doctor’s ofce or exitng the consultaton room, or leaving the pharmacy. Draw dummy tables of desired data based on the checklist to ensure that all informaton required can be captured. Where possible, every item should be designed to be answered, even if this is in a negatve way, e. Check content validity with experts in the area – verify that important areas are addressed appropriately 16. Pre-test the checklist on recorded sources which are similar to (but not part of) the study populaton to ensure: a. Test-retest reliability: This is checking if the same person will answer the same way on repeated testng on diferent days. Inter-rater reliablity: This is checking to see if items checked by diferent data collectors yield the same answers. Usually you use one checklist per recorded source, though you may use a tabulated checklist for multple sources. Here you observe and record data, unlike in recorded sources where you extract data. Data capture can be done directly by an observer or by pre-recording (camera/audio) followed by an assessment. For structured observaton, you need to develop a checklist of all the data to be observed that will answer your research objectves. For unstructured observaton, there are no instructons etc on how and what to observe. This means that people being observed are not aware of being observed or not aware of what they are being observed for. Check that you know the contents of the checklist just before the observaton commences. Only when you use a recording device (camera/audio) can you extract data afer the event. When you apply a “Trojan horse”, the false study will have to be explained to the respondents later. The informal group situaton and open-ended nature of the questons are intended to encourage partcipants to comment on behaviour and elaborate on opinions to an extent that is more difcult in more formal individual interview situatons. He/she should not show support or objectons to any opinion discussed, either verbally or non- verbally. Note-taker: a competent individual who records the discussion verbatm (in the words of the respondents). Audio-recording device: consent has to be taken from partcipants before this can be used. Moderator introduces subsequent topics as the discussion progresses, making sure each topic has been adequately explored. Additonal questons may arise that need to be asked when exploring an area to obtain in-depth informaton. Moderator summarises the topics that have been discussed, closes the session and thanks partcipants. In order to avoid confusion in the use of terms, the following table points out the distncton between techniques and tools applied in data collecton. Interview/self-administered Interview schedule/checklist; questonnaires, questonnaire audio-recording device 2. Observaton eyes, pen/paper, watch, scales, microscope, checklist, video camera etc 4. Pilot: the process of carrying out a preliminary study, or a component of the study, going through the entre procedure with a small sample. What are the limitatons, weaknesses, tme and resource requirements of the technique? Preferably limit the number of data collectors so as to reduce error in data collecton. Train immediately prior to data collecton to avoid memory lapse and loss of data collectors from the research project. This promotes team work; diferent people raise diferent issues and they can learn from each other; it standardises training for all. Duraton of training depends on the size/number of the tools and be sufcient to allow for role play and feld experience. Make sure that the data collectors and supervisors all have a clear understanding of the study and methods. Supervisors need additonal training supervision of data collectors, quality control and project management. This can be done by directon observaton or by repeat observaton/interview of same respondent and comparing with earlier data collected. Decide the sofware you want to use for data entry and for data analysis (see Pros & Cons of Database Packages). Dummy tables are blank tables that clearly show what data will be collected and how comparisons will be made. Dummy tables help to: • ensure that the data you collect will answer the queston you pose.