New Autoimmune Diseases Cure
The risk of reactions to antilymphocyte globulin is increased in patients with autoimmune disease (126). Fever and chills, sometimes with extreme hyperpyrexia, nausea and vomiting, urticaria, and reduced platelet and granulocyte counts were reported after the administration of horse antithymocyte globulin. Infusion of intravenous immunoglobulin 0.14 g kg in 17 patients with autoimmune diseases, in whom circulating immunoglobulins had been depleted, was associated with a high incidence of serious adverse effects (94). Treatment was terminated in four patients because of adverse effects, including urticaria, severe hypotension, arthralgia, and chest discomfort.
The cholinesterase inhibitors are used in the treatment of Alzheimer's disease (tacrine, 7-methoxytacrine, done-pezil, metrifonate, and rivastigmine), the treatment and diagnosis of myasthenia gravis (distigmine, edrophonium, neostigmine, physostigmine, prostigmine, and pyridostig-mine), and the treatment of atony of the intestine or bladder. In the eye, they increase the flow rate of aqueous humor across the trabeculum, reduce resistance to its flow, and consequently lower the intraocular pressure.
Recently, Mikuriya (1999) reported on interviews of 1800 patients who used marijuana for various medical conditions. Of these patients, he reported that 41 experienced analgesia following traumatic inflammation induced pain, autoimmune disorder-induced pain and ideopathic pain. Similarly, Consroe et al. (1997) found self-reported reductions in pain in patients with multiple sclerosis. Consroe et al. (1998) found similar self-reported pain reduction in patients with spinal cord injury. Schnelle et al. (1999) used an anonymous standardized survey of the medical use of cannabis and cannabis products of patients in Germany, Austria and Switzerland. Data from 128 170 patients were usable. Of these, 5.4 used cannabis for back pain and 3.6 for headache. Table 2.2 lists human studies of cannabinoid effects on pain.
The aminoglycosides are contraindicated in patients with hypersensitivity to aminoglycosides. The amino-glycosides should not be given to patients requiring long-term therapy because of the potential for ototoxic-ity and nephrotoxicity. One exception is the use of streptomycin for long-term management of tuberculosis. These drugs are contraindicated in patients with preexisting hearing loss, myasthenia gravis, parkinson-ism, and during lactation or pregnancy. Neomycin, amikacin, gentamicin, kanamycin, netilmicin, and tobramycin are Pregnancy Category D drugs the remainder are Category C.
Many oncogenic signaling pathways are controlled by PI3-K and phos-phatidylinositol phosphate 3'-phosphate (PTEN), so it would seem likely that there would be potential benefit from developing inhibitors of the PI3-K PKB-signaling cassette (42-44). The first evidence for the role of PI3-K in cellular transformation came from studies showing the association of PI3-K activity with the oncogenic proteins polyoma middle-T antigen and Rous sarcoma pp60v-src (45,46). Later, the analysis of the avian sarcoma virus genome identified an ortholog of p110a that was capable of transforming chicken embryo fibroblasts and inducing hemangiosarcomas in chickens (47). A truncated form of the regulatory subunit p85a, termed p65, has been isolated from a murine thymic lymphoma cell line (48). The p65 p110a complex is constitutively active, and transgenic mice expressing p65 in T-lymphocytes develop a lymphoproliferative disorder and renal autoimmune disease (49). Another mutated form of p85a has been...
Muscle weakness after botulinum toxin injection is usually due to local spread of the agent. Asymptomatic systemic effects have been detected in patients with cervical dystonia after repeated botulinum toxin injections, when muscle biopsies from the vastus lateralis muscle were examined (11). However, generalized neuromuscular symptoms are rare. Patients with a reduced margin of safety with regard to neuromuscular transmission might be considered prone to systemic effects, but even in patients with myasthenia gravis symptoms distal from the injection site have been reported only occasionally (12). However, generalized muscle weakness can occur if higher doses of botulinum toxin are used, and a recent report has illustrated that this may happen in patients after many uneventful treatment sessions (13). Electrophysiological findings in these patients were suggestive of mild botulism, with doses of botulinum toxin of 600-900 units. Two similar cases had been reported previously (12)....
In the presence of neuromuscular disorders, such as myasthenia gravis or Lambert-Eaton syndrome, botulinum toxin-induced inhibition of acetylcholine release can cause generalized weakness (17). Therefore, botulinum toxin should, if at all, be used with extreme caution in patients with neuromuscular disease, who have a reduced margin of safety with regard to neuromuscular transmission.
In the beginning, determining the dosage that will control symptoms may be difficult. In many cases, the dosage must be adjusted upward or downward until optimal drug effects are obtained. Patients with severe symptoms of the disease require the drug every 2 to 4 hours even during the night. Sustained-released tablets are available that allow less frequent dosing and help the patient to have longer undisturbed periods during the night.
In autoimmune diseases cyclophosphamide can cause menstrual disorders (oligomenorrhea or sustained amenorrhea) and ultimately sterility or premature menopause. This has been particularly exemplified in lupus erythematosus, and several studies have shown a high prevalence of menstrual disorders or premature ovarian failure in cyclophospha-mide-treated patients, or a significantly higher incidence of both complications compared with other immunosup-pressive regimens or healthy controls (31-33).
In inflammatory or autoimmune diseases, both daily oral and cyclic pulse intravenous cyclophosphamide regimens are used, but it is unclear whether one route of administration should be preferred to another. The cumulative dose obtained in those given an intravenous pulse regimen is consistently lower than in those given daily oral administration, and the incidence of bladder cancer or infection is expected to be lower in the former. However, the choice of the maintenance regimen remains a dilemma as regards efficacy and toxicity (73). For example, in one study in 50 patients with Wegener's granulo-matosis there was a similar overall incidence of adverse effects in patients treated with prednisone plus oral cyclo-phosphamide compared with those who received predni-sone plus intravenous pulse cyclophosphamide (74). Patients in the oral group had a higher incidence of severe or fatal infectious complications, but a lower incidence of cumulative relapse rates at 4.5 years.
Clinical use of reversible inhibitors is directed to eye, skeletal muscle, neuromuscular junctions, gastrointestinal tract, urinary tract, respiratory tract, and heart and used in treatment of glaucoma (an ocular disease caused by increased intraocular pressure due to inadequate drainage of aqueous humor at filtration angle), myasthenia gravis (an autoimmune disease
The transmission of viral infections by immunoglobulins has occasionally been suspected. However, intravenous immunoglobulin preparations are considered relatively safe, and there are no reports of transmission of HIV or hepatitis B (44,101). This is probably because of the high degree of viral inactivation of the cold ethanol fraction-ation and the screening of every donation for several viruses, such as HIV and hepatitis B and C (85). Of 56 patients with autoimmune diseases who received 167 infusions of intravenous immunoglobulin, none developed antibodies to human immunodeficiency virus and hepatitis C virus or hepatitis B surface antigen (12).
EGCG is also beneficial for treating endocrine and autoimmune disorders. This polyphenol alters the production of a number of hormones, including those involved 49. Hsu SD, Dickinson DP, Qin H, Borke J, Ogbureke KUE, Winger JN, Camba AM, Bollag WB, Stoppler HJ, Sharawy MM, Schuster GS (2007) Autoimmunity 40 138
A number of reports have confirmed that interferon alfa can induce or unmask underlying silent myasthenia gravis (SED-13, 1097) (SEDA-20, 327) (SEDA-21, 370). The diagnostic criteria for myasthenia gravis were clearly fulfilled in these reports, and an autoimmune reaction was the most likely mechanism, as each patient had positive serum anti-acetylcholine receptor antibodies and required permanent anticholinesterase drugs long after interferon alfa withdrawal. Myasthenia gravis developed in two patients treated with interferon alfa-2b for chronic hepatitis C, one of whom also took ribavirin (76,77). Both had an increase in acetylcholine receptor antibody titers and required permanent pyridostigmine and immunosuppres-sant treatment. These findings suggest that interferon alfa does not cause myasthenia gravis but unmasks it.
Mephobarbital is to be avoided if a person has porphyria, a disease reflecting a body chemistry disorder and in which a person may be harmed by exposure to light. The drug should also be avoided if a person has a muscle-weakening disease called myasthenia gravis, or a thyroid deficiency causing an affliction called myxedema.
The cholinesterase inhibitors are contraindicated in patients with hypersensitivity to the drug or any components of the drug. Some of these products contain sulfites, and patients with sulfite sensitivity may experience allergic-type reactions. The drugs are also contraindicated in patients with any active inflammatory disease of the eye and during pregnancy (demecarium, Pregnancy Category X echothiophate iodine, Pregnancy Category C) and lactation. The cholinesterase inhibitors are used cautiously in patients with myasthenia gravis (may cause additive adverse effects), before and after surgery, and in patients with chronic angle-closure (narrow angle) glaucoma or those with narrow angles (may cause papillary block and increase the angle blockage). When the cholinesterase
The elderly and patients with hepatic disease are more likely to experience adverse effects and toxicity to benzodi-azepines due to their reduced metabolism of these agents. Caution should also be used in prescribing these agents for patients with COPD and sleep apnea, a history of substance abuse, cognitive disorders, renal disease, CNS depression, porphyria, and myasthenia gravis.
Undoubtedly, inflammation is also an immune response. Drugs described in other chapters, such as antihistamine agents, nonsteroid anti-inflammatory agents, antiserotonin drugs, and many others can also be formally grouped with immunopharmacological agents. However, only the drugs having a direct effect on cells that have immune functions, such as lymphocytes, plasma cells, and subtypes of these cells will be examined in this chapter. It should be noted that the vital functional products of these cells themselves, such as lymphokines, interferons, and interleukins, are very important immunopharmacological drugs. The immune system has an enormous number of antigens that differentiate between 'own' and 'alien' molecules. It plays a huge role in autoimmune diseases, hypersensitivity reactions in the body to certain irritants, and in transplant rejections.
The author of the editorial found fault with the fact that the US experts have based their recommendations on the slimmest of evidence. The main human study was a self-recall series of 172 patients presenting to a private practice in London (9). In a letter to the editor, Beckett (10) pointed out that daily doses of 200 mg or less have been taken by millions of people worldwide for several decades without evident toxicity and that testimonials from clinicians expert in the use of pyridoxine have attested to its safety in these doses (11). Referring to the editorial, the author of the study in question stated that their study referred to 172 women with raised blood concentrations of pyridoxine that reverted to normal within 4 days of stopping pyridoxine, and was not a self-recall series.'' In a recent follow-up of these women who had raised blood concentrations, compared with controls from the same practice who had had a blood test in 1985-86 and whose record showed that they were not...
ACTH is used cautiously in patients with diabetes, diverticulosis, renal insufficiencies, myasthenia gravis, tuberculosis (may reactivate the disease), hypothyroidism, cirrhosis, nonspecific ulcerative colitis, heart failure, seizures, or febrile infections. The drug is classified as a Pregnancy Category C drug and is used cautiously during pregnancy and lactation. ACTH is used cautiously in children because it can inhibit skeletal growth.
In the case of insulin the effectors and second messenger are not known. It has been established that hormone deficiency effects can exist even in the presence of above-normal levels of hormone. The receptors appear to be resistant to the hormone. One likely reason for this is decreased receptor availability as well as lowered sensitivity by them. Several diseases are believed to involve the development of antibodies to membrane receptors, so they do not function normally toward their ligands. Among such autoimmune diseases are myasthenia gravis, multiple sclerosis, and possibly schizophrenia.
Drug abuse is a problem of increasing worldwide significance. In addition to the obvious socioeconomic problems associated with the use of so-called street drugs, the abuse of ethical pharmaceuticals may also result in serious untoward health effects depending upon a wide range of variables (Chiang and Goldfrank 1990). One possible medical complication of drug abuse is modulation of the immune system, or immunotoxicity (Pillai and Watson 1990). The immune system is a highly regulated organ system that presents a variety of potential targets for modulation by drugs. This modulation may take the form of immunosuppression, leading to an enhanced susceptibility to infection or neoplasia conversely, it may take the form of immunostimulation, resulting in hypersensitivity (allergy) or autoimmunity (Luster and Rosenthal 1993). Closely associated with drug abuse in recent years has been the emergence of the acquired immunodeficiency syndrome (AIDS), a retroviral infection spread by sexual...
Because retinol deficiency results in keratini-zation of epithelial tissue, at one time retinol was recommended for skin conditions including acne. There is no clinical evidence that retinol is effective for skin conditions. Now that it is realized that the active form is retinoic acid, the focus has been on developing pharmacologically active compounds based on this structure. These are divided into treatment of three groups (1) acne, (2) the autoimmune disease psoriasis, and (3) malignancies.
The corticosteroids arc grouped according to their capacity for Na+ retention, their effects on carbohydrate metabolism, and their anti-inflammatory effects. Thus, glucocorticoids have pleoiotropic effects and arc used in clinical practice in (as well as replacement therapy in cases of adrenal insufficiency) treating diverse diseases such as inflammatory rheumatic disorders, asthma, autoimmune diseases (systemic lupus erythematosus and others), acute kidney transplant rejection, and allergic and skin diseases. In pregnant women at risk for preterm birth, corticosteroids are also used for the induction of lung maturity. High doses of daily glucocorticoids are usually required in patients with severe diseases involving major organs, whereas alternate-day regimens may be used in patients with less aggressive disease. Intravenous glucocorticoids (pulse therapy) are frequently used to initiate therapy in patients with rapidly progressive, inmunologically mediated diseases (Rournpas 1993)....
Mitoxantrone is active in breast cancer, acute promyelocitic or myelogenous leukemias, and androgen-independent prostate cancer. Although early reports seemed to indicate that its cardiotoxicity was lower than that of the anthracy-clines,56 this claim has been subsequently challenged.57 Mitoxantrone has been recently approved for treatment of secondary progressive multiple sclerosis (MS).58 The rationale for this application stems from the fact that MS is considered to be an autoimmune disease where a heightened immune action results in the destruction of the myelin of the central nervous system, causing nerve impulses to be slowed or halted and leading to the symptoms of MS. Since chemotherapeutic
Protection from the degradation processes described above, two examples being the nitroimidazole derivatives azathioprine (imuran) and thiamiprine (guaneran). These compounds act as prodrugs and are presumably activated by an SNAr mechanism involving nucleophilic attack from thiols onto the 5 position the 4-nitroimidazole ring, followed by elimination of the thiopurine as a leaving group (Fig. 2.39). None of these prodrugs are more effective as anticancer agents than the parent compounds although azathioprine is an important immunosuppressant agent, widely used in autoimmune diseases.49
Adverse effects, prevention and treatment, 17.28 interactions, 16.13, 18.30 intoxication, prevention and treatment, 17.29 monitoring therapy, 18.25 mortality, 19.14 urinary system, 19.16 Local anesthetics, see Anesthetics Lyme disease vaccine, autoimmune disease, 24.366 allergic reactions, antibiotics, 23.251 angio-edema, ACE inhibitors, 22.225 autoimmune disease, Lyme disease vaccine, 24.366
JAK3 is mainly found in lymphoid cells, and appears to be stimulated only by activation of cytokine receptors containing the yc subunit (IL-2, -4, -7, -9, -13, -15, -21 receptors). Therefore, inhibition of JAK3 results in immunosuppression by blocking the T-cell mitogenic signal. Besides their potential as antineoplastic agents, JAK3 inhibitors may find application as immunosuppressive drugs to control autoimmune diseases and transplant rejection.
After it was revealed that there was no solid evidence of a link between silicone breast implants and autoimmune disease, the FDA should have probably followed the advice of its advisory panel and allowed their sale again. However, the FDA sent the manufacturers back to do more studies to make doubly sure. Fair enough they are not depriving people of an important medication. But in the case of emergency contraception it is estimated that close to 51,000 abortions were averted in 2000 through its use and there have been no serious adverse side-effects reported. Since emergency contraception is only available with a doctor's prescription (except for six states), that number would likely skyrocket and it is estimated that close to 700,000 abortions could be averted. That would be a serious victory for anti-abortion advocates and for women who would not have to go through an invasive procedure or take RU-486, which can induce significant
The complex of azathioprine-associated multisystemic adverse effects is referred to by the misnomer azathioprine hypersensitivity syndrome.'' This well-characterized reaction has been described in numerous case reports and includes various symptoms which can occur separately or concomitantly they comprise fever and rigors, arthralgia, myalgia, leukocytosis, cutaneous reactions, gastrointestinal disturbances, hypotension, liver injury, pancreatitis, interstitial nephritis, pneumonitis, and pulmonary hemorrhage (SED-13, 1121) (SEDA-20, 341) (SEDA-21, 381) (SEDA-22, 410) (7). Isolated fever and rigors are sometimes observed, and severe renal and cardiac toxicity or leukocytoclastic cutaneous vasculitis are infrequent. Symptoms usually occur within the first 6 weeks of treatment and can mimic sepsis. The initial febrile reaction is often misdiagnosed as infectious, and could be associated with acute exacerbation of the underlying disease, for example myasthenia gravis (SEDA-21, 381)...
As another minor point, the use of catalytic antibodies with esterase activity could theoretically lead to autoimmunity against endogenous enzymes. This problem could be partially overcome if Fab fragments were used, or perhaps completely overcome if humanized antibodies or their fragments were used. Also, it is not currently known if endogenous ligands will be substrates for these catalytic enzymes this could potentially decrease the effective rate for cocaine metabolism or lead to other medical problems.
Methotrexate (a methyl derivative of aminopterin, which is also called amethopterin) has a half-life of 12-24 hours, but approximately 5-35 is stored for several months as polyglutamate derivative in hepatocytes and erythrocytes (Hendcl 1984). It is used for a wide range of indications - for example, to terminate ectopic or unwanted pregnancies, and for the treatment of autoimmune diseases, chronic inflammatory diseases, and neoplasias. Methotrexate carries a teratogenic risk, with a similar pattern of malformations to aminopterin (see above), so that sometimes reference is made to an aminopterin methotrexate syndrome (Bawle 1998). However, in view
Patients with muscle disorders (dystrophia myotonica, myotonia congenita, myasthenia gravis, and hyperkalemic periodic paralysis) tend to react unpredictably to suxa-methonium. In myasthenia gravis, small doses of suxamethonium may be tried and the resulting effect monitored. In the other diseases listed non-depolarizers, cautiously used, are preferable. Cardiac arrest has been reported in patients with pseudohypertrophic muscular dystrophy (Duchenne type) and excessive muscle damage may be produced by suxamethonium in this condition. In myasthenia gravis responses to suxamethonium are unpredictable (265-268). Resistance has been reported and the development of a phase II block can occur more readily, occasionally leading to prolonged paralysis. The measures used to treat the condition, for example
The traditional use of plants such as B. pilosa might confer beneficial effects by increasing nonspecific defense mechanisms. Bioactive compounds that stimulate the immune system are useful as adjuvants in the treatment of certain bacterial, fungal, and parasitic diseases in addition immunosuppressive compounds may be useful in situations in which immune responses are undesirable, such as transplant rejection, autoimmune diseases, or allergies.
Cannabidiol (CBD) is a natural constituent of Cannabis sativa that is not psychoactive (Benowitz et al. 1980 Perez-Reyes et al. 1973b Pertwee 2004), but possesses pharmacological activity that is being explored for therapeutic applications (Pertwee 2004). CBD has been reported to be neuroprotective (Hampson et al. 1998), analgesic (Holdcroft 1984 Karst et al. 2003 Vaughan and Christie 1984), sedating (Holdcroft 1984 Melamede 1984 Plasse 1984 Vaughan and Christie 1984), antiemetic (Plasse 1984), anti-spasmodic (Baker et al. 2000), and anti-inflammatory (Malfait et al. 2000). In addition, it has been reported that CBD blocks the anxiety produced by THC (Zuardi et al. 1982) and is useful in the treatment of autoimmune diseases (Melamede 1984). These potential therapeutic applications alone warrant investigation of CBD pharmacokinetics, but also, the controversy over whether CBD alters the pharmacokinetics of THC in a clinically significant manner needs to be resolved (Agurell et al. 1984...
Classical examples of pharmaceutical products are Physostigma veneno-sum Balf. (Calabar bean), Myroxylon balsamum (L.) Harms (Tolu basalm) and Glycyrrhiza glabra L. (liquorice). Physostigma venenosum Balf. contains physostigmine which is used to treat myasthenia gravis and primary glaucoma. Physostigmine is structurally close to acetylcholine and inhibits the enzymatic
ALS is a devastating neurological disorder characterized by selective upper and lower somatic, but not autonomic, motor neuron degeneration leading to paralysis and eventually death. Other functions such as intellectual abilities and sensory perception are preserved. Several theories regarding the patho-genesis of ALS have emerged including glutamate excitotoxicity, free radical oxidative stress, neurofilament accumulation and autoimmunity (see Parsons and Danysz 2002 for review).
TNFa was originally identified because of its antitumor activity. However, later studies have shown that this cytokine plays a major role in autoimmune diseases and is also involved in multiple activities, including metastasis, viral replication, septic shock, inflammation, and fever.
Quinine is contraindicated in patients with known hyper-sensitivity. The drug is also contraindicated in pregnant women (Pregnancy Category X) and in patients with myasthenia gravis (may cause respiratory distress and dysphagia). Quinine absorption is delayed when administered with antacids containing aluminum. Plasma digitalis levels may increase when digitalis preparations and quinine are given concurrently. Plasma levels of warfarin are increased when administered with quinine.
Immunoglobulin solutions contain primarily immunoglobulin-G (IgG) antibodies, and are produced from pooled human plasma. The extent to which IgG antibodies pass through the placenta is dependent on the gestational age, the dosage, the length of treatment, and the kind of preparation given. However, Fab fragments do not pass (Miller et al. 2003). Immunoglobulins are used for different maternal or fetal indications - for example, in cases of antibody deficiency or infectious diseases (especially as a preventive measure), to improve the symptoms of some maternal autoimmune diseases, or to treat the symptoms of some fetal conditions (such as, for instance, heart block in the fetuses of mothers with lupus erythematosus).
Still not clear, but in idiopathic thrombocytopenic purpura an early fall in platelet-associated IgG and IgM may be a primary event, due to interference with antibody binding by platelets (22). Several other mechanisms of action of intravenous immunoglobulin in autoimmune diseases have been suggested, such as enhanced suppressor activity, Fc receptor blockade on neutrophils and macrophages (23), inhibition of complement activation and modulation of anti-idiotype responses (24), cytokine modification, neutralization of superantigens, and regulation of T cells and the idiotypic network (16,25). The suppression of polyclonal immunoglobulin biosynthesis induced by high-dose immunoglobulin infusions has also been suggested as a possible mechanism (26).
Rituximab is a chimeric anti-CD20 monoclonal antibody that has become important in treating non-Hodgkin's lymphoma and is being tried in other B cell malignancies. There has also been recent interest in its use to treat autoimmune diseases. Severe reactions are rare, but are seen in patients with bulky tumors or with leukemic involvement with high numbers of CD20 positive cells (99c, 100c). It has been suggested that this is due to a tumor lysis syndrome and that complement activation can play a pivotal role (101E).
Weegink CJ, Chamuleau RA, Reesink HW, Molenaar DS. Development of myasthenia gravis during treatment of chronic hepatitis C with interferon-alpha and ribavirin. J Gastroenterol 2001 36 723-4. 17. Carella C, Mazziotti G, Morisco F, Manganella G, Rotondi M, Tuccillo C, Sorvillo F, Caporaso N, Amato G. Long-term outcome of interferon-alpha-induced thyroid autoimmunity and prognostic influence of thyroid autoantibody pattern at the end of treatment. J Clin Endocrinol Metab 2001 86 1925-9.
Direct injection to tissue is a common approach for cationic lipid-mediated gene therapy. Intratumoral injection of DNA-liposome complexes containing either E6 or E7 antisense plasmid resulted in significant growth inhibition of C3 tumors grown in a syngeneic mouse model (185). E6 and E7 are two onco-genes responsible for the maintenance of the malignant state of HPV-position tumors. Nabel et al. (186) have directly injected recombinant pDNA containing murine class I major histocompatibility (MHC) gene into localized arterial segment of various major organs and showed that the direct gene transfer by liposomal transfection did not lead to treatment related toxicity, autoimmunity, or gonadal localization of the transgene in mice. The toxicity
In the past 30 years, numerous publications have appeared on use of pyridostigmine and neostigmine during pregnancy for the treatment of the autoimmune illness myasthenia gravis. According to these experiences, the use of these cholinergics has not been associated with congenital malformations or other adverse effects (review by Tellez-Zenteno 2004, Batoechi 1999). In 10-15 of babies born to mothers with myasthenia gravis, transient signs of neonatal myasthenia are noted, which are apparently caused by the placental transfer of receptor-blocking antibodies and not associated with the cholinergic therapy. In a few cases, placental transfer of receptor-blocking antibodies results in fetal neonatal arthrogryposis multiplex congenita (AMC) (Polizzi 2000).
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