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The effect of water-soluble vitamin E on cyclo- sporine pharmacokinetics in healthy volunteers buy 100 mg viagra sublingual overnight delivery erectile dysfunction treatment thailand. Single nucleotide polymorphisms in human P-glycoprotein: its impact on drug delivery and disposition buy cheapest viagra sublingual erectile dysfunction natural remedies at walmart. I: A model for studying the passive diffusion of drugs over intestinal absorptive (Caco-2) cells generic 100mg viagra sublingual visa erectile dysfunction in teens. Applications of the Caco-2 model in the design and develop- ment of orally active drugs: elucidation of biochemical and physical barriers posed by the intestinal epithelium. Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability. Caco-2 cell monolayers as a model for drug transport across the intestinal mucosa. Transport and permeability properties of human Caco-2 cells: an in vitro model of the intestinal epithelial cell barrier. Evidence for a polarized efflux system for peptides in the apical membrane of Caco-2 cells. Epithelial polarity, villin expression, and enterocytic differentiation of cultured human colon carcinoma cells: a survey of twenty cell lines. The influence of culture time and passage number on the morphological and physiological development of Caco-2 cells. Identification of a novel route of extraction of sirolimus in human small intestine: roles of metabolism and secretion. Kinetic profiling of P-glycoprotein- mediated drug efflux in rat and human intestinal epithelia. P-Glycoprotein (P-gp) mediated efflux in Caco-2 cell monolayers: the influence of culturing conditions and drug exposure on P-gp expression levels. Radioligand-binding assay employing P-glycoprotein-overexpressing cells: testing drug affinities to the secretory intestinal multidrug transporter. Characteristics of the large neutral amino acid transport system of bovine brain microvessel endothelial cell monolayers. Bovine brain microvessel endothelial cell monolayers as a model system for the blood-brain barrier. Polarity of the blood-brain barrier: distribution of enzymes between the luminal and antiluminal membranes of brain capillary endothelial cells. Changes in brain microvessel endothelial cell monolayer permeability induced by adrenergic drugs. Angiotensin peptide regulation of fluid-phase endocytosis in brain microvessel endothelial cell monolayers. Application of cultured endothelial cells of the brain microvasculature in the study of the blood-brain barrier. Adsorptive endocytosis and membrane recycling by cultured primary bovine brain microvessel endothelial cell monolayers. P-glycoprotein as the drug efflux pump in primary cultured bovine brain capillary endothelial cells. Use of rhodamine 123 to examine the functional activity of P-glycoprotein in primary cultured brain microvessel endo- thelial cell monolayers. Functional expression of the P-glycoprotein mdr in primary cultures of bovine cerebral capillary endothelial cells. Mrp1 multidrug resistance-associated protein and P-glycoprotein expression in rat brain microvessel endothelial cells. Multidrug resistance-related trans- port proteins in isolated human brain microvessels and in cells cultured from these isolates. Transport of cyclosporin A across the brain capillary endothelial cell monolayer by P-glycoprotein. Restricted transport of cyclosporin A across the blood-brain barrier by a multidrug transporter, P-glycoprotein. Novel experimental parameters to quantify the mod- ulation of absorptive and secretory transport of compounds by P-glycoprotein in cell culture models of intestinal epithelium. Rhodamine 123 requires carrier-mediated influx for its activity as a P-glycoprotein substrate in Caco-2 cells. Development, validation and utility of an in vitro technique for assessment of potential clinical drug-drug interactions involving P-glycoprotein. In vitro p-glycoprotein inhibition assays for assessment of clinical drug interaction potential of new drug candidates: a recommendation for probe substrates. Retention of vital dyes correlates inversely with the multidrug-resistant phenotype of adriamycin-selected murine fibrosarcoma variants. Relationship between cytotoxic drug response patterns and activity of drug efflux transporters mediating multidrug resistance. Reciprocal correlation between expression of P-glycoprotein and accumulation of rhodamine 123 in human tumors. Rhodamine efflux patterns predict P-glycoprotein substrates in the National Cancer Institute drug screen. Transport of rhodamine 123, a P-glycoprotein substrate, across rat intestine and Caco-2 cell monolayers in the presence of cytochrome P-450 3A-related compounds. Inhibitors of P-glycoprotein-mediated dauno- mycin transport in rat liver canalicular membrane vesicles. The function of Gp170, the multidrug-resistance gene product, in the brush border of rat intestinal mucosa. Characterization of the regional intestinal kinetics of drug efflux in rat and human intestine and in Caco-2 cells. Role of P-glycoprotein as a secretory mechanism in quinidine absorption from rat small intestine. Effects of intestinal and hepatic metabolism on the bioavailability of tacrolimus in rats. Possible involvement of multiple P-glycoprotein-mediated efflux systems in the transport of verapamil and other organic cations across rat intestine. Functional expression of mouse Mdr1 in an outer membrane permeability mutant of Escherichia coli. Functional complementation of yeast ste6 by a mammalian multidrug resistance mdr gene. Expression of human P-glycoprotein in yeast cells–effects of membrane component sterols on the activity of P-glyco- protein. Photometric microtiter assay of inorganic phos- phate in the presence of acid-labile organic phosphates. Human jejunal effective permeability and its correlation with pre- clinical drug absorption models. Hepatobiliary disposition of valproic acid and valproate glucuronide: use of a pharmacokinetic model to examine the rate-limiting steps and potential sites of drug interactions.

Benzodiazepine positives were found in conjuction with ethanol in 25 to 78% of the cases buy generic viagra sublingual 100mg online impotence grounds for annulment. For impaired driving cases the presence of benzodiazepines ranged from 1 to 30% with the additional finding of ethanol ranging from 22 to 100% viagra sublingual 100mg with visa new erectile dysfunction drugs 2011. Studies that focused on profession transportation reported very low incidences of benzodiazepine use order viagra sublingual in india erectile dysfunction pump demonstration. In one study, only 1 of 317 participants (88% compliance) was benzodiazepine positive and had a prescription for its use (76). In the other study, none of the 822 (81% compliance) par- ticipants was positive for benzodiazepines (77). In 1398 mandatory postaccident cases studied for the Federal Railroad Association, only 2 benzodiazepine positive cases were detected, 1 with prescription for its use (78). In 7 of the 10 studies that did not include commercial drivers, etha- nol was a cofactor in greater than 50% of the cases. Benzodiazepine-positive findings along with other drugs were described in a few of these studies. In a study of impaired drivers in California published in 1979, 14 of the 56 cases positive for chlordiazepoxide also had phenobarbital (79). Louis published in 1987, 10 and 8 of the 30 benzodiazepine-positive cases were also positive for barbiturates or opiate analgesics, respectively (80). In a study in Sweden published in 2000 of 486 impaired drivers that had tested positive for codeine or dextropropoxyphene, 346 were also positive for a benzodiazepine (81). In a study from Washington state published in 2001, 4 of 29 zolpidem-positive cases were also positive for benzodiazepines (82). Drug Interactions with Benzodiazepines 29 Table 14 Effect of Analgesics and Anesthetics on Benzodiazepine Pharmacodynamics Agent Benzodiazepine Dose Agent Dose Time N Reference Methadone Diazepam 20 & 40, or 100 & 150% maintenance 0 h 5m 83 40 mg diazepam and 150% maintenance dose induced changes in pupil constriction and subjective opioid effects greater than those by either drug alone. Diazepam 10, iv 50–75 mg 0 h 50/50 87 No difference in sedation noted, but patients more comfortable with procedure. Drug Interactions with Benzodiazepines 31 methadone on the pharmacokinetics of diazepam. Propoxyphene is an extensively used analgesic; its coadministration with benzodi- azepines would not be uncommon. In a single study, subjects took three different ben- zodiazepines, oral alprazolam and intravenous diazepam and lorazepam, each one twice. In one setting, no other drug was taken; in the other, propoxyphene was administered every 6 h from 12 h prior to the benzodiazepine and then for the duration of the study (85). Coadministration of propoxyphene significantly inhibited the elimination of alpra- zolam; there was a slight, but nonsignificant inhibition of diazepam; and no effect on the pharmacokinetics of lorazepam (Table 15). No information was found on the in vitro inhibition of P450s by propoxyphene, but these data would support an inhibitory effect of propoxyphene on P450 3A4 that spares P450 2C19. No data were presented on the effect of propoxyphene on the pharmacodynamics of benzodiazepines. When midazolam or diazepam is combined with the opioids papaveretum, pethi- dine, or morphine during anesthesia, potentiation of the sedative or subjective effects is consistently found (86–88; Table 14). The combination of midazolam or diazepam with fentanyl has also been consis- tently found to result in potentiation of the sedative and in some cases respiratory depres- sant effects of the drugs (89–93). In the latter two studies, which used midazolam, sta- tisitical evaluation of dose responses suggested that the drugs interacted in a synergistic manner (92,93). A similar finding was found for combined use of diazepam or midazo- lam with alfentanil, including the synergistic response with midazolam (91,94–96; Table 14). A similar pharmacokinetic study has not been done with alfentanil, but both are P450 3A4 substrates (98–101) and may have similar potential to inhibit midazolam metabolism, as has been found in vitro for fentanyl (102). The interaction between naltrexone, an opioid µ receptor antagonist, and diaze- pam is another exception to the studies between anesthetics. Naltrexone was found to increase the negative mood states such as sedation, and decrease the positive mood effects such as friendliness of diazepam (Table 14), with no effect on its pharmacokine- tics (Table 15; 103). The interaction of the structurally unique anesthetic propofol or the barbiturate thiopental with midazolam has also been reported to have synergistic effects on the sedative effects of the drugs (Table 14; 104–107). This is consis- tent with the in vitro inhibition of midazolam metabolism by propofol (109). Clinical studies confirm that additive interactions occur between the opioids and other anesthetic agents. The synergistic response appears to occur when there is also a pharmacokine- tic interaction resulting in the inhibition of the benzodiazepines’ clearance. Chlordiazepoxide 5, or 3/d ´ 2 d 45 mL 6f,12m 388 Subjects were tested on mental and then psychomotor performance starting at +1h. Pharmacodynamic and Pharmacokinetic Interactions with Ethanol The effect of combined use of ethanol on pharmacodynamic end points has been studied with a large number of benzodiazepines (Table 16). In general, ethanol has a potentiating effect on some of the psychomotor and subjective measures, but rarely affects all such measures in any one study. In part because the studies were not designed to detect it, synergistic effects were not noted. Because of the diverse end points in the studies, there was no apparent general set of pharmacodynamic end points that etha- nol consistently had an effect upon. Ethanol was reported as enhancing impairment of reaction time for alprazolam (110), clobazam (111), diazepam (112), and tofisopam (112), whereas it had no effect on reaction time with bromazepam (113), loprazolam (114), oxazepam (115), nordi- azepam (115), and temazepam (115). It is therefore difficult to draw conclusions about some ben- zodiazepines being more susceptable to the interactive effects with ethanol. Drug Interactions with Benzodiazepines 33 Table 16 (continued) Dose Ethanol Ethanol Benzodiazepine (mg) Dose Time N Reference Clobazam 20, or 77 g 0–1. Clorazepate 20, or 1 g/kg 14m 389 Enhance alcohol acute euphoric effects and decreased dysphoric effects in the following morning. Diazepam 5, or 3/d ´ 3 d 42 mL 0 h 20 390 Measured ability for cancellation of letters, digit substition, addition and pegboard placement begining at +75 min. Diazepam 2, or 3/d ´ 2 d 45 mL 6f,12m 388 Subjects were tested on mental and then psychomotor performance starting at +1 h. Ethanol enhanced the effects on two of nine mental tests; no effect on psychomotor tests. Tofisopam 100, or ´ g/kg 12m 112 Enhanced impairment on coordination, reaction, flicker fusion, maddox wing and attention tests. When ethanol was given 3 h after alprazolam, only minimal effects were found (116). When ethanol was given only 45 min after alprazolam, however, it had additive effects on most of the end points measured (110). Similarly, combining ethanol with diazepam at the same time led to enhanced impairment of reaction time (112), whereas giving the ethanol 3 h after diazepam did not (116).

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These supplements can also protect your tissues (eyes cheap viagra sublingual american express erectile dysfunction treatment forums, kidneys buy viagra sublingual american express impotence and age, blood vessels) from the damage diabetes often causes purchase viagra sublingual with american express erectile dysfunction drugs names. They can also support your immune system, protect your heart, and improve circulation. The effectiveness of these supplements is not at all theoretical, but rather is fact. There are thousands of published studies proving the beneficial effects these supplements have on diabetics. Cinnamon Cinnamon is the brown bark of the cinnamon tree, which when dried, rolls into a tubular form known as a quill. It is available in either its whole quill form (cinnamon sticks) or as ground powder. According to cellular and molecular studies conducted at the University of California, Santa Barbara, Iowa State University and the U. Upon further examination, he isolated cinnamon as the substance in the apple pies that was preventing the diabetes. Their study included 60 Pakistani volunteers (30 men and 30 women ranging in age from 44 to 58 years) with type 2 diabetes, who were not taking insulin. For 40 days, groups 1, 2 and 3 were given 1, 3 or 6 grams of cinnamon per day, while groups 4, 5 and 6 received placebo capsules. The results were quite remarkable:  All three of the groups given cinnamon showed reduced blood sugar levels. In their latest paper, published in the Journal of Agricultural and Food Chemistry, Anderson et al. Additionally, Graves found that cinnamon is a very powerful antioxidant with the ability to neutralize free radicals, often elevated in diabetics, helping to minimize oxidative stress which plays such a big role in the disease. Some scientists had been concerned about potentially toxic effects of regularly consuming cinnamon. The latest research shows that the potentially toxic compounds in cinnamon bark are found primarily in the lipid (fat) soluble fractions and are present only at very low levels in water soluble cinnamon extracts, which are the ones with the insulin-enhancing compounds. Alpha Lipoic Acid Alpha Lipoic Acid (also known as thioctic acid or lipoic acid), is a very powerful, natural antioxidant; and is the single most important supplement you can take to treat diabetes. Although the body makes some alpha lipoic acid, it is not enough for optimal nutrition. In these foods, it actually occurs as lipolylysine though, and not actual lipoic acid itself. This means you would have to eat over two pounds of broccoli to get one single milligram of lipolylysine to convert into alpha lipoic acid. The journal BioFactors (volume 10, 1999) published a study conducted at the Eberhard- Karls University in Germany titled "Thioctic Acid-Effects on Insulin Sensitivity and Glucose- Metabolism". The researchers pointed out that "Thioctic acid is a co-factor of key mitochondrial enzymes, involved in the regulation of glucose oxidation, such as the pyruvate dehydrogenase and the alpha-ketoglutatarate dehydrogenase, both enzyme complexes which are known to be diminished in diabetes. They concluded "The clinical and experimental data indicate that this compound has beneficial effects on insulin sensitivity, correcting several metabolic pathways known to be altered in type 2 diabetes, such as insulin stimulated glucose uptake, glucose oxidation and glycogen synthesis. Results like this are far more than any pharmaceutical drug, anywhere on earth, at any cost. Nerve damage or neuropathy effects over 50% of diabetics and is one of its most damaging complications. In 2001, Nutrition 17 published a study which was conducted at the University of Southern California, titled "Molecular Aspects of Lipoic Acid in the Prevention of Diabetes Complications". These are rather powerful statements coming from very well respected research groups. It works to make insulin more effective by "bridging" insulin to cell membranes, thus increasing the number of active insulin receptors, resulting in increased insulin sensitivity. The trace mineral chromium is found in skin, fat, muscle, brain and adrenal glands. Chromium absorption through the small intestine is very poor; so normally, a lot of it gets excreted in urine. People with diabetes excrete even more chromium than healthy people; and the loss of this vital nutrient makes it harder for their bodies to respond to insulin. Studies show that chromium supplements can help both Type 1 and Type 2 diabetics control their blood sugar. The picolinate form of chromium called "chromium picolinate" is the most absorbable. It is a unique molecule that combines chromium with picolinic acid, a compound found in breast milk, which helps the body better absorb and process minerals. In addition, Chromax®; has demonstrated that it is significantly more bioactive than other forms of chromium. Vandium (vanadyl sulfate) is a trace element that exhibits a variety of significant insulin- mimetic properties. Clinical trials indicate that "in vitro", vanadium salts have most of the same major effects of insulin on insulin-sensitive tissues. Favorable results are seen, as well, in animal models of insulin deficiency, where vanadium significantly reduces blood glucose levels, and in insulin- resistant diabetic animals, where vanadium improves glucose homeostasis. In "in vivo" animal studies, examining the relationship between hyperinsulinemia, insulin resistance and hypertension, vanadium compounds produce significant, sustained decreases in both plasma insulin concentration and blood pressure. Clinical trials with vanadium compounds have produced benefits in both type 1 and type 2 diabetic patients. Six type 2 diabetic subjects treated with 100 milligrams of vanadyl sulfate daily for four weeks had significant reductions in fasting plasma glucose; beneficial effects on insulin sensitivity persisted for up to four weeks after vanadium treatment ended. Banaba Leaf Banaba (Lagerstroemia speciosa) is a plant native to India, Southeast Asia and the Philippines and has several medicinal uses. In many cultures the banaba leaf is brewed into a tea and used as a treatment for diabetes and as a weigh loss aid. Banaba Leaf Extract provides a blood sugar lowering effect similar to that of insulin in that it induces glucose transport from the blood into body cells. Recently, researchers have isolated an active ingredient in the banaba leaf called corosolic acid which was originally thought to be "the" blood sugar regulating substance in the leaf. Other researchers have found that corosolic acid may not be the only active ingredient in banaba leaves. A study published in the journal Planta Medica in 2001 compared a whole- leaf extract of banaba with insulin in cell cultures. Another study reported that banaba leaf extract contains at least three active ingredients that effect blood sugar. In animal studies, administration of banaba leaf extract resulted in a significant decrease of blood glucose. The same studies suggest that corosolic acid may stimulate glucose transport into tissue. In other animal studies, administration of banaba leaf extract resulted in reduced weight gain, reduced triglyceride accumulation and reduced adipose tissue, with no changes in diet.

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Parenteral drugs must not be prepared in advance of their immediate use (except when prepared by the Pharmacy) viagra sublingual 100 mg otc discussing erectile dysfunction doctor. Parenteral medicines do not routinely need to be double-checked by another practitioner; however buy viagra sublingual online from canada impotence exercises for men, each practitioner should check their own organisation’s policy on this matter before administering a medicine generic 100mg viagra sublingual with mastercard erectile dysfunction exercises dvd. It is good practice to request a double check on administration if: * The infusion involves the addition or mixing of drugs, e. Local circumstances may make involvement of a second practitioner desirable in order to min- imise the potential for error, e. Each practitioner is responsible for maintaining his or her own knowledge on all drugs. Information on such products can be found in the monographs of this book, in the package insert and/or via the Pharmacy department. Accountability Parenteral therapy is a common and important part of the care received by many patients. In order to protect patients and provide staff withthemeanstodeliversafeandeffectivetreatment,thepractitionershouldalwaysfollowguidance issued by their own organisation. In order to provide comprehensive patient care all nurses/midwives are expected to achieve competency at the earliest opportunity following appointment and may be called on to demonstrate their competency at any time. Although nurses/midwives can decline to perform duties in which they do not feel competent, they are obliged to adapt to new methods and techniques of adminis- tering medications and must work at a level commensurate with the grading of their role. Parenteral therapy, in particular, is an area that is continually evolving and can be considered to be an integral part of thenurse’s or midwife’s role and thus every effort must be made to achieve competencein this area of practice. All practitioners have a duty of care to their patients, who are entitled to receive safe and competent care. If a practitioner is asked to perform a duty which is outside their area of expertise they must obtain help and supervision from a competent practitioner until they and the Trust consider they have acquired the requisite knowledge and skills. A ppendix 3 U sual responsibilities of individual practitioners The prescriber1 * The prescribing of parenteral medicines or fluids is the responsibility of a doctor, or an indepen- dent or supplementary prescriber. The prescription must clearly state: * Approved name * Dose and frequency of the drug * Method of administration and by which route -- central or peripheral, intramuscular, subcuta- neous, etc. Venflon, is appropriate for the needs of the individual patient and the drug to be administered. The pharmacist1,2 The Pharmacist (or Pharmacy service) has the role of: * Monitoring the safety of the drug use process and alerting prescribers and other health care professionals to potential problems. The practitioner administering the parenteral drug3 For in-patients the practitioner preparing and administering the drug (not the second checker) must: * Appropriately identify the patient by checking their name and hospital identification number on an identity band (or an alternative as defined within the organisation’s patient identification policy) before administering the drug. A ppendix 4 A dvantages and disadvantages of parenteral therapy There are many advantages to using the parenteral route to administer medicines, but because of the potential risks to the patient the practitioner should always carefully consider all advantages and disadvantages before using the parenteral route. Disadvantages include: * Risk of infection * Dangerous and/or fatal if given incorrectly, e. A ppendix 5 Injection techniques and routes Intermittent intravenous infusions Thisisthetechniqueusedtoadministeraninjectabledruginanintravenousinfusionoveraperiodof time ranging from 20 minutes to several hours. The infusion may be connected to the primary intravenous giving set or to a secondary adminis- trationsetviaaY-connector. Administrationcanalsobeviaanin-lineburette,whichwould normally constitute a section of the primary giving set. The volume of intravenous fluid used to dilute the drug ranges from 50mL (the smallest intrave- nous fluid bag) up to 500mL. In clinical practice most drugs are given in 100mL and are set to infuse over 20--30 minutes. Advantages include: * A volumetric pump can be used to deliver the dose in a controlled way. These concentrations are used because they are isotonic with blood and thus do not cause haemolysis of blood cells. The drug to be given may be compatible with one or both of these, although solubility and stability times may differ. Infusion bags may contain about a 5% overage so the practitioner must take this into account if only using part of the bag. Mixing drugs in infusion bags is not advised without compatibility data, which can be found in reference sources such as the latest edition of Trissel’s Handbook on Injectable Drugs1 or via a website such as MedicinesComplete (www. Appendix 5 Injection techniques and routes | 885 Direct intravenous injections Some drug products may be administered directly into the venous circulation in a relatively small volumeof fluid over less than 5minutes. The injection may be given: * Via an injection port in an infusion line * Via an indwelling cannula, e. A direct intravenous injection (as opposed to an intravenous infusion) is used when: * Administration is urgent (e. Unless specifically directed otherwise by the manufacturer, a direct intravenous injection is given over 2--3 minutes, observing the patient and the injection site for signs of adverse reaction. The volume of injection is usually 5mL or less, although larger volumes may be necessary if the drug has low solubility, is likely to be an irritant to thevein or requires relativelyslow administration. Bolus injections into indwelling cannulas should always be preceded and followed by at least 2-- 5mL of a flushing solution. Some drugs are too irritant or toxic to be administered as a concentrated injection; for example, erythromycin is too painful and irritant to the vein, while potassium chloride 15% injection is too toxic to the myocardium in high concentration (and also extremely irritant). Intramuscular injections Intramuscular injections are administered into the muscle beneath the subcutaneous tissue, and are generally absorbed faster than subcutaneous injections. They are most commonly given into the thigh or the gluteal muscle, and occasionally into the deltoid muscle (which attaches the upper arm to the shoulder). The volume given at any one site is usually limited to 5mL for the thigh (or 4mL if it is a depot injection because depots can be more irritant), and 2mL for the deltoid muscle. If a series of injections are to be administered, injection sites should be used in rotation and a record of these kept. The two most common ways of giving an intramuscular injection are by: * Direct injection straight into the muscle, with the needle held at a 90 angle to the skin. Upon removal, pressure should be applied to the injection site to prevent leakage. This has the effect of sealing the injection under the skin and preventing leakage into the subcutaneous tissue. Relative bioavailability There may be bioavailability differences between intramuscular and intravenous administration of certain drugs, and the intramuscular route is usually associated with a delayed onset of action. It is therefore incorrect to assume that a drug dose is interchangeable between the intravenous and intramuscular routes. It is also considered to be an unsafe prescribing practice to specify alternative routes for the same prescription entry on a prescription chart. Subcutaneous injections of fluid are used to administer vaccines and medications, e. Appropriate sites for a subcutaneous injection include: * The outer aspect of the upper arm * The anterior aspect of the upper arm * The abdomen below the costal margins to the iliac crests * The anterior aspect of the thigh * The ventrodorsal gluteal area * The scapular area. The site must not be bruised, tender, hard, swollen, inflamed or scarred as this may hinder absorption and cause discomfort and injury to the patient.

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