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Externally order malegra dxt once a day erectile dysfunction clinic, belladonna is used in spinal tenderness purchase cheapest malegra dxt and malegra dxt erectile dysfunction drug stores, with congestion malegra dxt 130mg lowest price impotence trials, also in congestive occipital headaches and lumbago. It is applied in all conditions inducing a lame back and in neuralgia of the spinal and sacral nerves. In violent acute inflammation, it acts as a sedative and anodyne while it exercises its healing properties. It is used in rheumatism, in sprained and painful joints, and in boils and carbuncles. In this form, it is of value in spasmodic urethral stricture and in painful congestive conditions of the rectum. In the treatment of phlebitis, for which we have very few specific remedies, the late Professor Clark, because of its power in overcoming hyperemia of the venous capillaries and venous walls, claimed that belladonna, in the form of a strong ointment made from the concentrated extract and kept hot, would produce very prompt results. He would watch for the physiological effect—the dryness of the mouth, dilatation of the pupils, and dry throat; he would then remove it for a while, subsequently to reapply it in the same manner. Ellingwood’s American Materia Medica, Therapeutics and Pharmacognosy - Page 67 Atropine. Description—It occurs as a white crystalline body, usually in minute acicular crystals, or as an amphorous white powder of a bitter, acrid, nauseous taste and odorless. It is soluble in 130 parts of water and three parts of alcohol, fifty parts of glycerine and quite freely in ether and chloroform. Description—This salt is perhaps more commonly used in medicine than the unsaturated alkaloid, atropine. It is freely soluble in water and in alcohol, nearly insoluble in ether and chloroform. These alkaloids are of much advantage in narcotic poisoning and as stimulants in the recovery of patients from shock. The 1/100 of a grain will produce the physiological symptoms in a healthy patient. Atropine is used to dilate the pupil in examination of the interior of the eye, and it is useful in acute inflammation of that organ. It empties the capillaries of an excess of blood, abating the inflammatory processes. It prevents adhesions in iritis, and assists in breaking up any that may have occurred. Two grains of atropine are dissolved in an ounce of distilled water, or better yet, in an ounce of castor oil deprived of its ricinic acid. Atropine is of superior advantage, used hypodermically, in certain Ellingwood’s American Materia Medica, Therapeutics and Pharmacognosy - Page 68 emergencies; in narcotic poisoning, and as a stimulant in the recovery of patients from shock. The 1/ grain dose will produce the physiological 100 symptoms in a healthy patient. Within recent years, the action of atropine given hypodermically for controlling hemorrhage has gained so many advocates that it has now become established as a most reliable remedy for that purpose. His arguments have been unanswerable until its position is now fairly established. Doctor Paulding, writing in The Medical Council, relates some experiments with the hypodermic injection of atropine in acute alcoholism. There were eleven boys less than 12 years old playing in a freight-yard, where some high wines in barrels were standing on open cars. A barrel was tapped with a gimlet and through a straw all of the boys drank freely of the spirits. This is the characteristic indication for atropine, determined its use, and he gave a hypodermic of 1/ grain. The doctor reports two other cases where death seemed imminent but which were saved by a single hypodermic injection of 1/ 100 grain of atropine. Doctor Shadid dissolves 1/ of a grain of atropine in 2 ounces of water 60 and gives one teaspoonful every ten minutes until there is relief, in certain headaches which follow prolonged worry, excessive mental exertion, with more or less exhaustion. In acid stomach, where the hypersecretion of the acids is great, atropine, an occasional dose as needed, has been found to exercise a good influence. The use of cactus in subnormal temperatures has strong advocates, but its Ellingwood’s American Materia Medica, Therapeutics and Pharmacognosy - Page 69 influence is positively enhanced by combining it with atropine, giving the two in comparatively full doses for a time. The injection of atropine at the constriction, in case of hernia, or the application of the extract of belladonna over the enlarged hernia, has caused the spontaneous reduction in a number of cases. Description—In the formation of Homatropine the chemical process consists of the decomposition of the amygdalate of tropine by hydrochloric acid. Therapy—The agent is not advised for internal administration, although in doses of 1/ of a grain it has been given for excessive night sweats. It 20 is used in the, determination of refraction, and in examination, in ophthalmic practice. Its advantage is in its promptness of action as a mydriatic and its transient influence. It is used in the strength of four grains of the salt to an ounce of distilled water. A few drops instilled into the eye and repeated a few times, a few minutes apart, will in a short time accomplish the desired result. The effects are completely dissipated in the course of about thirty-six hours, while atropine retains its influence for, perhaps, ten days, and hyoscyamine for six or eight days. The main objection to the use of homatropine is the hyperemia of the conjunctiva which follows its use. Ellingwood’s American Materia Medica, Therapeutics and Pharmacognosy - Page 70 In the treatment of inflammations it is not as serviceable as atropine. Because of the increased engorgement of blood in the part, it increases the condition. A further advantage of atropine over this agent in inflammations is its permanency or persistency of action. As a nerve stimulant and permanent tonic, this valuable agent was comparatively unknown, when the first edition was issued. The writer took the responsibility of introducing it here through the confidence acquired by observing its prompt and satisfactory action during an experience of twenty years in the treatment of nervous diseases. There are many well-known and lauded agents that are hardly to be compared with this for prompt action upon the nervous system. Fifteen drops, three or four times daily, well diluted, will usually meet the case. It should, however, never be given in larger quantities than twenty minims unless the patient is thoroughly accustomed to the remedy, and has found the usual dose insufficient. Otherwise there is danger of obtaining the physiological effect of the drug, which is announced by pain at the base of the brain. When this symptom makes its appearance the medicine should be discontinued for a day or two, and then given in reduced doses. If administered in hot water during the day, its action is much quicker, and in cold water at night on retiring it has a more extended influence. Physiological Action—Its selective influence is directly upon the brain Ellingwood’s American Materia Medica, Therapeutics and Pharmacognosy - Page 71 and upon the nutritive functions of the organism, increasing nerve force and improving the nutrition of the entire system.

It is a destruction of the pancreas (specifically the islets) by the pancreatic fluke which is attracted to the pancreas by wood alcohol discount malegra dxt on line erectile dysfunction stress. Zap flukes and eliminate wood alcohol as described in the section on diabetes (page 173) order malegra dxt amex erectile dysfunction drugs in the philippines. Use no artificial sweetener and no beverages besides milk discount 130 mg malegra dxt with amex erectile dysfunction age 16, water and the recipes given in this book. They are well motivated to pre- vent the need for giving themselves daily shots of insulin. Fried potatoes with 2 eggs (use only butter, olive oil or lard), 1 cup hot or cold milk. Cream of rice, with homemade “half n half” or whipping cream, cinnamon and vitamin C stirred in. Fruit cup, large bowl of peeled, chopped mixed fruit with whipping cream and 1 tbs. Green beans with potatoes, meat dish, cabbage apple salad, water with lemon juice and honey, 1 cup hot milk. Fresh green beans, especially fava beans contain a sub- stance that is described in old herbal literature to be espe- cially beneficial to diabetics. Potatoes (not overcooked), peeled to make sure there are no blemishes (contain mold and pesticide) can be cooked with the beans. Add fresh chopped parsley to the sauce or butter for both green beans and potatoes. Fresh parsley has special herbal goodness (high magnesium, high potassium, diuretic. Canned meat is safe from parasites but may have smoke flavoring added (contains benzopy- rene) or nitrates. Purchase the flip-top cans to avoid eating metal grindings from the can opening process. Add finely chopped apples (peeled) and a few apple seeds and whipping cream for the dressing. The drinking water should always have a little vitamin C, lemon juice or vinegar added, and 1 tsp. Asparagus, potato, raw salad, fowl dish, fruit, water with vinegar and honey, 1 cup hot milk. Fresh chopped chives may be added but no regular sour cream since this is very high in tyramine, a brain toxin. For dessert, fresh fruit chunks dipped in a homemade honey sauce (honey, water and cinnamon). The fruit may be chopped with whipping cream, cinna- mon and honey sauce (not more than 1 tbs. Acid foods stimulate; spices and B-vitamins (especially B ) stimulate; hot foods1 stimulate. Toxins at either location (especially food-derived toxins) tell the body to stop eating. Asparagus, meat dish, white rice (brown rice contains mold), coleslaw, milk, water, ice cream. A hot meat dish (no pasta, no wheat flour, no regular gravy) can be fried, cooked or baked, but not grilled. If more bread is requested, provide a wheat-free, corn-free variety; but limit bread eating to “after main dish” eating. If not enough milk is drunk: make custard pudding or rice pudding so the daily amount (3 cups) is consumed. There is no fruit or vegetable juice except homemade, and not much of that because it crowds out milk and water. If by chance, your elderly person hates these and starves themselves to get your sympathy, add a lot more potatoes and rice (never brown) to raise calories. The heavy use of cream and butter is offset by no deep fat fried food and little cheese. The morning blood sugar test is essential to keep track of changing circumstances. Be careful not to use rubbing alcohol when making the finger stick (use vodka or grain alcohol). Or even just the knowledge they are staying well controlled and will never have to take insulin shots. Diabetic Supplements Several supplements are especially good for diabetics: • Fenugreek seeds, 3 capsules with each meal. Maybe they have something in them that helps detoxify wood alcohol, since bilberry leaves are good for eyes, too. Diabetic Eating Out Since the rules are always somewhat relaxed when “eating out” a diabetic loved one will badger you to go out with them. If rules are sure to be broken, calculate it into the rest of the day so you can compensate for it. Ethnic foods often had to be given up when children were raised (switched to hot dogs and pizza) but with this diversion gone, a return to family food would be most welcome and most healthful. And they certainly were made at home where cleanliness and “persnickitiness” are at their finest! Good advice is to return to old fashioned home cooking: with its flour and butter, lard and cream, homemade pasta, olive oil and soup, coarse cereal grains and plain fruit. Gone are the fruit juices, flour mixes, crackers and sweets that fill grocery shelves. Time is the great inhibitor but if you have the means or the help, the best advice, nutritionally, is a return to old-fashioned cooking and recipes. Use her wooden spoons, glass glasses, and plain dishes, her wooden and straw bowls and enamel pots and pans. But a good salt rule is to either cook with it or have it on the table, but not both. Use aluminum- free sea salt, and make sure the salt is sterilized by heating five minutes at 400°F in a glass pie plate to kill mold. The best salt is a mixture of 1 part of your aluminum-free, sterilized sea salt and 1 part potassium chloride (another kind of salt, see Sources). Potassium ousts sodium (salt) from your body, so you can use twice as much of this kind of salt! It is important to find the poison as soon as you can since the rest of the body will soon be affected, too. It is a herculean task but only gets harder each day, so keep notes as you ask: Is there new carpeting?

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Diffuse pigmentary change may also present as melasma on the face due to either epider- mal melanin abnormalities or dermal macrophages containing melanin or heme pigment buy 130 mg malegra dxt with amex erectile dysfunction natural remedies at walmart. Hypomelanotic macules are vitiligenous and are frequently observed most prominently on the lower extremities buy 130mg malegra dxt overnight delivery erectile dysfunction cream 16. Dryness and surface roughness best order for malegra dxt erectile dysfunction caused by guilt, best perceived by tactile rather than visual means, are among the most common complaints related to aged and photoaged skin, but are not specific for either. Scaling due to dryness or perturbation in epidermal turnover is also common, but not specific to photodamage. Benign seborrheic keratoses are mostly cosmetic growths that appear in sun- exposed body areas. Grossly observed thinning and histological stratum corneum irregularity, epidermal thinning, and abnormal collagen and elastin result in skin that is easily traumatized with abrasions, cuts, and tears. Blood vessels can be easily seen through the skin and, because of epidermal thinning and decreased dermal integrity, the skin bruises and bleeds more easily than normal. Sensory decrease, not usually clinically obvious, has been partially docu- mented in increasing age, though not specifically in photoaging. Utilizing skin compliance and a two-point discrimination testing on the pad of the index finger, increasing age was correlated with decreased tactile sensitivity and said to be likely related to change in the nervous system (tactile discrimination), rather than change in skin itself (skin compliance) (5). An actual increase in intraepidermal nerve fibers, correlated with severity of photodamage, was observed in a recent study of the ultrastructure of photodamaged skin and was theorized to be indica- tive of a neural involvement in the pathophysiology and/or repair of photodam- aged skin (6). This complicated interaction continues to be an extremely important area of research (7). Since the products will be applied at least to the face, and probably to other areas of the body, it must be cosmetically acceptable and preferably refined or elegant. Exceptions are those individuals who will use a greasy oint- ment or malodored product thinking it must be therapeutic if it has those undesir- able characteristics. Product qualities and potential acceptance can be tested more rigorously by using a panel of trained individuals who note the various properties of the Photoaging 19 Table 4 Product Testing Product attributes by dermatosensory panel Claim substantiation Instrumentation Pharmaceutical testing formulation (Table 4). Even untrained individuals may be able to distinguish overall acceptability but use of trained panelists allows much greater refinement of the overall and individual aspects of the product. Commercial testing is avail- able (entitled the DermatoSensory Profile), which describes and grades or com- pares products for their characteristics of appearance and feel on the skin. Testing includes evaluation of the rate of absorption of the product into the skin, including spreadability and stickiness, immediate afterfeel, including shininess, greasy or oily feeling, drag (the sensation of resistance to motion over the skin), and residue (the sensation or perception of something remaining on the skin). Perception of residue after set periods of time such as 5, 15, and 30 min is called delayed afterfeel. Various descriptions of the product itself, aside from its characteristics on the skin such as color, odor, thickness, substantivity, consistency, grittiness, or smoothness can also be described. Many of these product characteristics are important in consumer acceptance of the cosmeceutical as well as in their percep- tion of benefit. Cosmeceutical Testing No matter if cosmetic or pharmaceutical endpoints are sought, adequate trial de- sign is critical for accurate, precise, consistent, reproducible, and valid observa- tions in photoaging. The optimum trial for pharmaceutical, and to some extent cosmeceutical, purposes is double-blind, placebo (vehicle)-controlled, multicen- ter, and frequently, for the chronic process of photoaging, of at least several months’ duration. Cosmetic testing may be of much shorter duration in fewer subjects but should optimally follow the same basic logic. Study of the parameter that is most important to the product is essen- tial; a facial moisturizer designed for older females living in the north should not be artificially tested in male and female college students in the south. Overall severity rating for study entry and follow-up of global appearance has been accomplished with a photographically derived rating scale, with 0 20 Cunningham Figure 1 none, 1 to 3 mild, 4 to 6 moderate, and 7 to 9 severe photodamage (8). These evaluations may be performed by the investigator, by the subject, or by third persons comparing photographs of before and after in a randomized and blinded manner. This and similar rating scales may also be applied at baseline and follow-up to specific parameters such as wrinkles, surface roughness, mottled pigmentation, overall color, skin dryness, and texture. A 100-mm visual analogue scale has been successfully utilized to rate the overall appearance of the skin and specific parameters of fine wrinkles, discrete pigmentation, shallowness, and texture. A clinical panel evaluation technique has been described that potentially allows precise, consistent, and completely unbiased evaluations of clinical state (9). Very high-quality photographic slides are obtained, prepared in matched ca- rousels, and placed on two random-access projectors in a rear-screen projection booth. Side-by-side comparison of each patient’s time-randomized baseline and end-of-treatment photographic slides by trained, but uninvolved, evaluators is thus accomplished in a completely blinded and randomized manner. Both global response and specific parameters of overall appearance, fine wrinkles, and dis- crete pigmentation can be judged and graded on a 13-point balanced categorical Figure 2 Photoaging 21 scale with zero representing no difference between the two photographs. A score of 1to 6 is assigned when the end-of-treatment photograph is perceived to be better and a score of 1to 6 when the baseline photograph is perceived to be better. Trials of isotretinoin have successfully utilized the clinical panel and dem- onstrated the therapeutic effect compared to vehicle (10,11). Claim Substantiation If the above-described pharmaceutically oriented trials demonstrate significant effect, claim substantiation may be relatively easy and clear-cut. However, distinction may be made among the various aspects of a claim for a product. There are, in each country, very different cultural and legal perspec- tives dictating what can be stated about a product designated for photoaging. These claims are generally related to the broad perception of whether the cosmetic or skin-care aspects, the potential cosmeceutical action, or a proven pharmaceuti- cal effect is being claimed and advertised. In this regard, everything from con- sumer statements, consumer panel testing, instrumentation results, clinical testing results, to absence or presence of statements regarding alteration of structure or function of the skin must be considered in evaluating, regulating, and advertising a product. Use of Instrumentation With no other methodology is there the same potential for accurate, precise, reproducible, consistent data to used appropriately or to be nefariously manip- ulated to purport therapeutic effect as with the now-available and sophisticated instrumentation (12). Evaluation of the obtained instrumental data must take place in a clinically appropriate context for them to be truthful and meaningful (Table 5). Table 5 Instrumentation Optical profilometry Fluorescent photography Ultrasound Transepidermal water loss Skin hydration by capacitance/conductance Laser Doppler Colorimetry 22 Cunningham Optical Profilometry Profilometry is one of the most useful techniques in photodamage evaluation. A skin replica obtained with silflo dental impression material is oriented and side- illuminated to produce shadows of various widths and depths that are captured by high-resolution video interfaced to a computer containing image-analysis soft- ware (13). The width and depth of the ‘‘peaks’’ and ‘‘valleys’’ of the skin surface may correspond to roughness, wrinkling, or other surface contours or markings and can be differentiated by the analysis software. The technique is reproducible and blinded, can be utilized even in large clinical trials, and has correlation with the clinical condition. Evaluation of the cheek and crows feet area of the face consistently demonstrate approximately a 10% improvement in wrinkles after treatment with tretinoin (14). It can also be useful in evaluation of skin roughness that may change after tretinoin or alpha hydroxy acid treatments. The photographs of photoaged skin may be highly dramatic in accentuating mottled and diffuse pigmentary alterations and may also be quantitative, utilizing visual counting of macules and evaluation of diffuse change compared to a 20-point gray scale (15). Polarized photography allows selective enhancement of the appearance of wrinkles, pigmentary change, or ery- thema (16).

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Interestingly buy malegra dxt 130 mg free shipping erectile dysfunction treatment in bangkok, only a few cases of toxicities to patients due to such drug-drug interactions have been reported purchase malegra dxt now erectile dysfunction causes diabetes, probably because most chemotherapy regimens are administered until some undesired toxic effect (e buy cheap malegra dxt online erectile dysfunction treatment centers. The same reasoning applies to cases of severe neurotoxicity when itraconazole is administered with vincristine (104,105). John’s wort) can markedly decrease the plasma concentrations of these drugs leading to decreased clinical efficacy, and inhibitors (e. John’s wort has been shown to significantly increase the clearance of indi- navir (117). Antidepressant Serotonergic Drugs and Sympathomimetics These two classes of drugs are subject to life-threatening interactions (e. Digoxin Digoxin is a narrow therapeutic index drug whose primary drug-drug inter- actions appear to involve the P-glycoprotein transporter (121). An additional drug-drug interaction may occur at the level of reduction of the lactone ring double bond by intestinal microbial reductases that yields an inactive metabolite. Some antibiotic drugs can kill these microbes and lead to increases in digoxin concentrations (122). Arylamine Sulfonamides and Hydrazine Drugs Several of these drugs can cause immune-mediated idiosyncratic toxicities, such as immune hemolysis, agranulocytosis, aplastic anemia, drug-induced lupus, and severe skin rashes (123,124). It is well known that for most drugs in these classes acetylation of the amine or hydrazine group protects against the toxic effects based on significantly higher incidences of toxicity in individuals that geneti- cally are slow acetylators (125). However, there are no reported drug-drug interactions with the N-acetyltranferases. Oxidation products of the arylamino or hydrazine groups are implicated as the haptenic reactive metabolites (123–131), and both cytochromes P450 and peroxidases have been implicated in the oxi- dation process (124,129,130). Although it might be anticipated that inducers and inhibitors of these enzymes would affect toxicities associated with the drugs, no reports of such drug-drug interactions on toxicity have appeared. This in part may reflect less attention given to these enzymes and/or lesser extents of induction and inhibition of these enzymes by drugs (chap. D),6- mercaptopurine is cleared by S-methylation catalyzed by the genetically poly- morphic thiopurine methyltransferase (134). This enzyme is inhibited by the drug sulfasalazine, leading to bone marrow suppression as a result of increased 6- mercaptopurine concentrations (135,136). Valproic acid is extensively glucuronidated, and the coadministration of valproate with other drugs eliminated extensively by glucuronidation, such as lamotrigine (137) and zidovudine (138), can significantly decrease the clearance of these latter two drugs with resultant toxicities. Sertraline has been found to cause a similar effect with lamotrigine (139) and fluconazole with zidovudine (138). Interestingly, increased incidences of convulsions observed when car- bapenem antibiotics are administered to patients on valproic acid may be caused by carbapenem inhibition of glycolytic enzymes that hydrolyze valproic acid glucuronide back to free valproic acid (140). However, in only a few cases have these interactions apparently increased the risk of hepatotoxicity, the major serious toxicity observed in humans who ingest this drug (142). In part, this may be a consequence of multiple pathways of metabolism for acetaminophen and, in part, because relatively high concentrations of the drug (>1 mM) are usually required to cause hepatotoxicity, which is an order of magnitude greater than therapeutic concentrations. Surprisingly, only a few cases of hepatotoxicity, caused by the use of normal doses of acetaminophen in patients on anticonvulsant drugs that are inducers of cytochromes P450, have been reported (143–150). This may be due to the ability of these same drugs to induce glucuronosyl transferases, which would increase the formation of acetaminophen glucuronide, a nontoxic metabolite (151,152). However, recent reports also show that some anticonvulsants can inhibit some glucuronosyl transferases involved in 698 Nelson acetaminophen glucuronidation (153,154). Furthermore, many inducers of drug metabolizing enzymes affect animals and humans differently, likely due to species differences in their orphan nuclear receptors (155,156). However, the induction is modest (2- to 3-fold); therefore, other susceptibility factors, genetic and others such as decreased glutathione stores and nutritional status, are likely to play an important role in some individuals (169–174). Most of these interactions occur at the level of metabolism, though interactions with transporters, such as P-glycoprotein, are also becoming better recognized. Unfortunately, we still do not have a good enough understanding either of the metabolism of some drugs or of mechanisms of toxicity (particularly idio- syncratic toxicities) to be able to predict whether or not a drug will cause toxic effects and under what conditions. For example, several nonsteroidal anti- inflammatory drugs have caused idiosyncratic toxicities that may be related to acyl glucuronide formation and/or cytochrome P450 activation (175–177). Therefore, it would be anticipated that other drugs that affect these pathways might either increase or decrease the risk of toxicities, but almost no data are available because of the idiosyncratic nature of the toxicities and lack of knowledge about susceptibility factors and/or immune system involvement in mechanisms leading to drug-induced toxicity. The same reasoning applies to hepatic injury caused by the drugs trovofloxacin (178) and troglitazone (179) that were removed from the market. There is very little published information about whether it was the drugs themselves or their metabolites that were responsible for the observed toxicities. However, new methods are beginning to provide useful information on structure/toxicity relationships that can be applied to safer drug design (180–182). In cases like that of mibefradil, the basic science of drug-drug interactions has progressed enough to make informed benefit/risk decisions. Thus, it is important to continue basic and clinical investigations of drug-drug interactions as well as studies of mechanisms of toxicity to effect safer drug therapy. Genomic identification of potential risk factors during acetaminophen-induced liver disease in susceptible and resistant strains of mice. A review of enzyme induction of warfarin metabolism with recommendations for patient management. Further insight into the stereoselective interaction between warfarin and cimetidine in man. Comparative effects of rantidine and cimetidine on the pharmacokinetics and pharmacodynamics of warfarin in man. Comparison of the effect of macrolide antibiotics erythromycin, clarithromycin and azithromycin on terfenadine steady- state pharmacokinetics and electrocardiographic parameters. Role of intestinal P-glycoprotein (mdrl) in interpatient variation in the oral bioavailability of cyclosporine. Concomitant administration of cyclo- sporin and ketoconazole in renal transplant recipients. Final conclusions of the National Lipid Association Statin Safety Assessment Task Force. Quantification and mechanism of the fluoxetine and tricyclic antidepressant interaction. Inhibition by paroxetine of desipramine metabolism in extensive but not poor metabolizers of sparteine. Very long half-life of paroxetine following intoxication in an extensive cytochrome P4502D6 metabolizer. Debrisoquine polymorphism and the metabolism and action of metoprolol, timolol, propranolol and atenolol. Celecoxib inhibits metabolism of cytochrome P4502D6 substrate metoprolol in humans. An immunochemical approach to identifying and characterizing protein targets of toxic reactive metabolites.