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This depolarization is called an action potential cheap extra super levitra 100 mg overnight delivery impotence due to diabetic peripheral neuropathy, and is carried first by sodium ions and then by potassium ions (see figure 4 safe 100mg extra super levitra erectile dysfunction only at night. The neuron is the fundamental anatomical unit of the brain; the action potential is the fundamental physiological (functional) unit of the brain. An action potential lasts only about a millisecond, during which time sodium rushes in and potassium rushes out through ion channel proteins opened by conformational change. The original ionic dis- equilibrium is then re-established through the rapid elimination of Na+ ions. In myelin- ated nerves, such ion exchange can occur only at the nodes of Ranvier, and the action potential jumps very rapidly from node to node without a loss of potential. This wave of depolarization passes along the axon to the nerve ending and can be repeated several hundred times per second. The action potential is the fundamental functional (physiological) unit of the brain and is the means of trans- mitting information within the nervous system. An action potential is generated by changes in the transmembrane voltage gradient across the neuronal membrane. The resulting wave of depolarization travels along the neuron as an electrical signal, transmitting information. Synaptic transmission is not electrical but chemical, and is triggered by the arrival of the action potential at the nerve ending. This causes a Ca2+ ion influx across the membrane and into the neuron, resulting in the release of an interneuronal chemi- cal messenger (neurotransmitter) characteristic for that particular neuron. There seem to be several different neurotransmitter release mechanisms, although none is well understood. When released, the neurotransmitter crosses the synaptic gap by passive diffusion and binds transiently to a receptor on the membrane of the postsynaptic neu- ron. The released neurotransmitter is then either destroyed enzymatically or taken back into the synapse and recycled. Inhibitory neurotransmitters, on the other hand, activate Cl− ion uptake through the postsynaptic neuronal membrane. This effect makes the intracellu- lar potential more negative than the original resting potential and thus hyperpolarizes the neuronal membrane. Naturally, a greater than normal impulse will be necessary to fire such a hyperpolarized neuron, since the threshold value of the action potential remains the same. Both excitatory and inhibitory impulses summate and trigger an all-or-none response of a particular neuron, on which hundreds of other neurons may synapse. Besides binding to postsynaptic receptors, a released neurotransmitter also “back- diffuses” to presynaptic receptors or autoreceptors on the neuron from which it was just released, fulfilling an important feedback regulatory function by facilitating or inhibit- ing transmitter release. It has been suggested that these presynaptic receptors are also heteroreceptors—that is, they respond to cotransmitters as well as neurotransmitters produced by the same neuron. For instance, it is known that neurotensin regulates the release of norepinephrine, its cotransmitter. Now that the fallacy of the “one neuron— one transmitter” dogma has been revealed, it is logical to assume that multiple trans- mitters (neurotransmitter plus a cotransmitter) may regulate each other’s release and metabolism in a given synapse and that there may be considerable overlap among presynaptic auto- and heteroreceptor functions. To be defined as a classical neuro- transmitter, a molecule must be synthesized and stored in a neuron, released from that neuron in a Ca2+ dependent process, diffuse to an adjacent neuron, specifically dock with a receptor on that adjacent neuron, and have its binding to this receptor blocked by a competitive antagonist. A neuromodulator, on the other hand, is a molecule which is present in the synaptic cleft and which modifies either the frequency or the efficiency of the neurotransmitter molecule, thereby either amplifying or attenuating the neuro- transmitter action. The traditional neurotransmitters have been recognized for a number of decades and include acetylcholine, norepinephrine, and glutamate. At this point it is well to consider that the classical definitions and concepts in this field have been undergoing considerable change, and that the distinctions between neurotransmitters, cotransmitters, neuromodulators, and neurohormones often become blurred. Many peptide hormones of the hypothalamus and hypophysis, for instance, have been recognized as having neurotransmitter activity at other sites, and neurohormones and the discipline of neuroendocrinology have become increasingly important in the biosciences. In recent decades, an explosive development in the discovery of cotransmitters has greatly expanded our understanding of neurotransmission, and of the homeostatic equi- librium that is regulated by aminergic and peptidergic cotransmitters even in systems as simple as that of Hydra. Postsynaptically, cotransmitters can influence the same recep- tor on the target, bind to two different receptors on the same target, or bind to two dif- ferent receptors on two different targets. This multipotential reactivity may explain the fact that some drugs and endogenous substances are partial agonists only: they may miss the help of a cotransmitter that the full agonist receives. Cross-reactivity of cotransmitter combinations may also explain the many side effects and shortcomings of neuroactive drugs that have been designed without the benefit of knowing the complete story of in vivo processes at the target. It should be kept in mind that a single synapse may operate with as many as four transmitters simultaneously, in any combination of amine and peptide, or even peptide and peptide, within the groupings shown. Amine neurotransmitters are synthesized in the synapse and are stored in small or large vesicles. Different populations of the same type of neurons may differ in their content of cotransmitters. The brain is really a collection of highly specialized components of enormous anatomical complexity. The brains of different mammals are very different, and the evo- lutionary changes in the brain are seen primarily as an increase in relative size and in the complexity of cortical folding, thus increasing the area devoted to association (i. The brain is divided into three gross parts: the brain- stem, the cerebrum, and the cerebellum. Structurally, the brain may be likened to a bou- quet of flowers with the cerebrum (as two cerebral hemispheres) “blossoming” outwards above the brainstem; the cerebellum is attached at the back of the brainstem. The brain consists of the brain stem (medulla oblongata, cerebellum, pons, mesencephalon, diencephalon) and the cerebrum (cerebral hemispheres, subcortical white matter, basal ganglia). Twelve pairs of nerves, collectively referred to as the cranial nerves, originate in the brainstem and sub- serve sensory and motor function in the head and neck. One of these nerves, the vagus nerve (so called because it wanders throughout the thorax and abdomen), is important to the autonomic nervous system (section 4. Within the medulla are a number of neurons actively involved in the biosynthesis of epinephrine (section 4. Lying partly in the pons and partly in the mesencephalon is the locus ceruleus (or nucleus pigmentosus), which is rich in norepinephrine-containing neurons and thus plays a role in the adrenergic neurotransmitter systems (see section 4. The dorsal (back) portion of the pons and mesencephalon is referred to as the tegmentum and contains a variety of nerve fibre tracts. The mesencephalon contains the substantia nigra, a region of the brain that is intimately involved with the dopamine neurotransmitter and is thus involved in the medicinal chemistry of Parkinson’s disease (section 4. The dien- cephalon is divided into the following regions: thalamus, hypothalamus, subthalamus, and epithalamus. The thalamus acts as a relay station that transmits, correlates, and integrates all ascending sensory information from the body on its way to the cerebrum. The hypothalamus has a regulatory influence over the autonomic nervous system and is the point at which the nervous system (using neurotransmitters as messengers) and the endocrine system (using hormones as messengers) interface.

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The efficacy of this regimen in such pregnancies is somewhat controver- sial (Edelin et al purchase 100mg extra super levitra johns hopkins erectile dysfunction treatment. Babies born to mothers on methadone cheapest extra super levitra erectile dysfunction treatment penile prosthesis surgery, as with heroin, may experience withdrawal symptoms. Furthermore, withdrawal symptoms of methadone-exposed infants are more severe than those of heroin-exposed infants, with more seizures and a greater number of days of displaying withdrawal symptoms in the maintained group (Blinick et al. In addition, it was found that fetal growth retar- dation is more severe among methadone-exposed infants than among heroin-exposed infants (Blinick, 1973), a finding that was not supported by other studies (Lifschitz et al. Methadone withdrawal using dose tapering employing adjuvants such as numbutal were not associated with adverse pregnancy outcomes in a more recent study in a large public hospital where a number of studies of substance abuse were undertaken (Dashe et al. The available information is often confounded by many factors, including poor maternal health, lack of prenatal care, malnutrition, presence of infectious diseases, and the use of a myriad of substances. The sections that follow are a summary of the known maternal-fetal effects of the 16 social and illicit substances most commonly used during pregnancy. This chapter concludes with a section that sum- marizes the complex issues that attend polydrug use during pregnancy. Each substance is described, highlights of human embryo-fetal risks are reviewed, and perinatal effects are defined. Specific social and illicit substances used during pregnancy 305 Alcohol use during pregnancy and maternal alcoholism Alcohol is a central nervous system depressant and its abuse during pregnancy has adverse effects on both the mother and the fetus. We found that the prevalence of drinking four or more drinks [2 ounces (59 ml) of absolute alcohol] per day was 1. The prevalence of fetal alcohol syndrome varies widely among countries and is estimated at one per 100 live births in northern France (Daehaene et al. It is estimated that as many as 5 percent of congenital anomalies may be due to maternal alcohol intake during pregnancy (Sokol, 1981), although precise estimates of alcohol-induced birth defects are difficult to ascertain. Alcohol abuse during pregnancy appears to be the most frequent known teratogenic cause of mental retardation (Abel and Sokol, 1987; Clarren and Smith, 1978). Maternal effects Alcohol abuse during pregnancy generally affects the course of pregnancy negatively and reported adverse pregnancy outcomes related to alcohol consumption include stillbirths, premature deliveries, decreased placental weight, and spontaneous abortion (Parazzini et al. Such outcomes may occur even at low levels of alcohol consumption – less than four drinks per day (Little, 1977; Plant, 1984; Sokol et al. Some studies on the effects of alcohol use of various durations during pregnancy has shown that occasional binge drinking by moderate drinkers did not negatively affect birth outcome (Autti-Ramo et al. Continuous drinking throughout pregnancy appears to cause fetal damage in a dose-dependent manner (Halmesmaki, 1988). In 306 Substance abuse during pregnancy addition, the frequency of sexually transmitted diseases and other infections is higher among women who abuse alcohol during pregnancy. These anomalies repeatedly occurred among infants born to women who were chronic alcoholics, drinking eight or more such beverages every day (Clarren and Smith, 1978; Larroque, 1992; Sokol et al. The investigators found that at 5 years of age the children whose mothers had continued drinking during pregnancy showed more alcohol-related deficits than non-alcohol- exposed children or children whose mothers stopped drinking in the second trimester of pregnancy. Transient withdrawal symptoms, including tremors, hypertonia, and irri- tability, were reported among infants born to women who chronically drank alcohol late in pregnancy (Coles et al. In addition, there is genetic polymorphism for alcohol dehydrogenase, implying a pharma- cogenetic etiologic role in the severity of effects. Importantly, medical and psychological support for cessation of drinking should be offered. Since many of these women may also abuse other sub- stances, they should also be advised to stop using these agents. Alcohol summary Fetal alcohol syndrome is one of the three leading causes of mental retardation. In addition, this syndrome is a leading cause of poor pregnancy outcome and childhood morbidity (congenital anom- alies, including mental retardation). Approximately 6 percent of pregnant women tested positive for methamphetamines at delivery in one study (Little et al. No studies are available regarding the illicit use of amphetamines during pregnancy. Several factors complicate extrapolation of these results to illicit use or abuse: (1) dose regimens in illicit use are not controlled; (2) they likely involve amounts much greater than those used therapeutically; and (3) harmful impurities (e. Methylphenidate (Ritalin), dextroemphetamine (Dexedrine) and a cocktail of ampheta- mine salts (Adderall) are stimulants with potential for abuse that are often represented as amphetamine or methamphetamine by those who distribute illegal drugs. However, preterm delivery and 308 Substance abuse during pregnancy perinatal mortality were increased in frequency (Eriksson et al. Follow-up of these children found that 15 percent were delayed in academic achievement in school, but other adverse effects were not reported (Eriksson et al. Medically supervised use of amphetamines during pregnancy is not convincingly asso- ciated with an increased frequency of congenital anomalies among several thousand infants exposed during the first trimester (Heinonen et al. Illegal metham- phetamines are known as ‘designer drugs’ because they are synthesized by methylating novel sites along the carbon chain and ring in a one-step reduction process. Sometimes methamphetamines are used to ‘cut’ or dilute other illicit drugs (cocaine). In 2006, they are called ‘club drugs’ because they are available in night clubs, and are used in parties called ‘raves’ that may last 24 hours or longer. The stimulant effects of methamphetamines keep the party-goers awake, although some vari- eties of this drug may cause hallucinations or other altered states of consciousness. Notably, the prevalence of methamphetamine use has not decreased over the past decade (Buchi et al. We reported 52 pregnancies complicated by methamphetamines finding that symmetric fetal growth retardation was increased above controls. The frequency of congenital anom- alies was not significantly increased (Little et al. Perinatal infant abnormalities and maternal pregnancy complications were not increased in frequency. The small sample size of the metamphetamine-exposed groups limits the ability to extrapolate these findings. Methamphetamines and cocaine use in pregnancy were associated with lower birth weight but not with anomalies (Oro and Dixon, 1987; Chomchai et al. Fetal growth retardation was associated with methamphetamine use throughout pregnancy, but when drug use was discontinued after the second trimester no difference in birth weight was found (Smith et al. Cannabinoid use during pregnancy 309 Lower birth weight was associated with maternal methamphetamine use during pregnancy among 47 infants in a study from Thailand (Chomchai et al. Medically supervised use of methamphetamines among 89 infants born to women who took the drug during the first trimester reported a frequency of congenital anom- alies no different from controls. Among 320 infants born to women who used the drug after the first trimester there were no abnormalities (Heinonen et al. The rele- vance of medically supervised use of methamphetamines to abuse employing much higher doses is not possible to assess. Frequencies of congenital anomalies (brain, anencephaly, eye, cleft palate) were increased among mice and rabbits whose mothers were given methamphet- amines during pregnancy at doses up to 20 times the therapeutic adult human dose (Kasirsky and Tansy, 1971; Martin et al.

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Such a journey is most unusual; assorted drugs have been moved from one schedule to another over the years cheap extra super levitra generic erectile dysfunction drug, but the direction is almost always to put the drugs under more controls rather than fewer best order extra super levitra impotence young. At sufficiently high levels, dextrorphan can make people feel as if they are intoxicated with alcohol. After male mice received dextrorphan in an experiment, they Dextrorphan 117 produced offspring having lower weight, delays in maturation, and abnormal swimming behavior. Whether the drug passes into a human fetus or the milk supply of a nursing mother is unknown. By the end of the twentieth century diazepam was one of the best- known antianxiety agents in America. Other medical uses of this fast-acting and long-lasting drug include treatment of insomnia, migraine, facial pain, muscle spasms, convulsions, vomiting, malaria, rattlesnake bite, alcohol and heroin withdrawal syndromes, cardiac difficulty created by cocaine, and mus- cle stiffness from tetanus and other causes. The body converts the drug into other chemicals, including temazepam and oxazepam. Unwanted actions of diazepam include weariness and weak- ness and occasionally headache, dizziness and vertigo, nausea, fuzzy or dou- ble vision, urinary control problems, and depressed mood. The compound can make users tired and impair vigilance, judgment, re- action times, and movement. A person using diazepam should be cautious about operating dangerous machinery; simulated driving tests demonstrate reduced ability after a dose. A study of newborn rats receiving the drug found that it slowed learning, but their learning capacity was normal even though the rats needed more time to learn something. Diazepam can interfere with the ability to recognize an angry ex- pression on someone’s face—a disability with distinct potential for social con- sequences—and a laboratory experiment demonstrated the drug’s ability to make people more aggressive if they are provoked. Diazepam is given to treat epileptic seizures, but long-term use can increase Diazepam 119 epileptic seizures. Among epileptics the drug can also cause status epilepticus, a potentially fatal condition in which seizures occur back to back. This mishap has been known to occur even when medical professionals administer the drug, and most rec- reational users lack training in anatomy. Intravenous injection of diazepam can stop breathing and heart action; when administering the drug intravenously hospitals are prepared for such emergencies, but most street users are not. In a small percentage of human volunteers (5% or less), rectal administration has produced euphoria, breathing difficulty, skin rash, runny nose, or diarrhea. Diazepam is one of the few drugs that can cause flat brain wave readings in a living person. Such readings are a classic sign of death, and medical personnel seeing such readings might decide to stop efforts that are keeping a patient alive. Among illicit drug users in the 1990s diazepam was the most common benzodiazepine. When researchers supplied recreational drug users with several benzodiazepine class substances, diazepam was rated as having the most abuse potential. In testing of the drug’s appeal, volunteers reported that the higher the dose, the higher the attractiveness. Researchers evaluating results of an experiment involving recreational drug users judged diazepam to be even more effective in producing pleasure than in producing medical effects. In one experiment with recreational drug users over one third of them de- scribed diazepam’s effects as reminiscent of barbiturates, which produce ef- fects similar to alcohol. Perhaps such effects explain why tests of drug preference show diazepam to be popular among moderate alcohol drinkers. Research indicates that euphoria from diazepam is more likely in a person with a family history of alcoholism. Moderate drinkers find diazepam more appealing than light drinkers do, but that may be due less to alcohol per se than due to a personality that finds drugs generally attractive. Humans can develop dependence with diazepam, causing a with- drawal syndrome if dosage ceases all at once instead of gradually. Depending on how much of the drug has been used for how long, withdrawal symptoms can be mild or strong. Mild cases may simply involve trembling, reduced appetite, and trouble falling asleep. In bad cases a person can experience per- spiration, muscle cramps and tremors, vomiting, and convulsions. Sudden stoppage of long-term diazepam dosage can provoke seizures, so doses need to be tapered off instead. Effect of a diazepam dose can be lengthened by propoxyphene and by the ulcer drugs omeprazole and cimetidine. The 120 Diazepam more tobacco cigarettes people smoke, the less drowsy diazepam makes them. Body weight also affects diazepam actions, with drug build-up and elimina- tion taking longer in bodies of fatter people. Experimenters have even found that drug effects can vary by time of day; at night diazepam prolongs the presence of an ibuprofen dose. Experimentation shows diazepam to have potential for causing cancer in mice, results causing researchers to suspect the same possibility in humans. Ex- amination of medical records from almost 13,000 diazepam users found no link to a higher cancer rate. Several other investigations found no connection between the drug and assorted human cancers, but results have been mixed on association with ovarian cancer. Hamsters receiving the drug during pregnancy can produce off- spring with cleft palate and other skull abnormalities. Diazepam experiments with rats have re- sulted in fewer pregnancies and higher death rates for pups. Some rat exper- iments produce birth defects and some do not; size of dose may be important. If pregnant mice receive the drug, their male offspring may have difficulty with sexual functioning as adults. They also may act more nervous than pups who lack fetal exposure, although rats that have no fetal exposure, but instead receive multiple doses soon after birth, act less uneasy in later life after dosage has stopped. A number of rodent studies find that prenatal ex- posure to diazepam may produce assorted behavioral effects that do not ap- pear until adolescence or adulthood. Those effects are measured by various tests (running mazes and the like) that are difficult to extrapolate to human experience, but the point is that diazepam’s effects may be unapparent in newborns and take years to emerge. A study of 689 pregnant women taking assorted antidepressants was unable to attribute any birth defects to diazepam, and the same results came from a smaller study; but nonetheless the drug is suspected of causing malformations. Measurements from pregnant women indicate that diazepam passes to the fetus and builds up there; blood levels of the drug in newborns can be higher than the mother’s. A case report notes severe multiple malformations in an infant whose mother used diazepam during pregnancy but does not establish cause and effect. Researchers tracked medical histories of several thousand women whose babies had major malformations and found an association between diazepam and cleft lip, the association becoming even stronger if women had smoked while taking diazepam during pregnancy. Additional research has associated diazepam with birth defects involving the heart, stomach obstruc- tion, and hernia.

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It is a common trouble spot because large parasites can attach themselves behind it and keep themselves safe from elimination buy discount extra super levitra line erectile dysfunction drugs not working. It is near this point where the appendix attaches and this order extra super levitra 100 mg without prescription l-arginine erectile dysfunction treatment, too, is a favorite location of pinworms. With an appendix full of pinworms and their bacteria, is it any wonder when it gets inflamed and causes pain? If there are any suspicions of appen- dicitis, zap pinworms and all enteric parasites and bacteria im- mediately. Because the current does not penetrate the bowel contents very well, zap every day for two weeks and take 2 tsp. Make sure bowel movements are regular after this (see the Bowel Program, page 546, for hints) and hands are washed after bathroom use and before eating. If appendicitis does not clear up it can lead to a burst appen- dix, spewing the dreadful contents into the abdomen. Kill pin- worms and roundworms and enteric parasites regularly (once a week) in children. Urinary Tract Pain Urinary tract infections, including bladder, kidney, and ure- thral infections, are easier to clear up than to test for. Make sure both of you clean up the urinary tract by zapping and doing the Kidney Cleanse. If dairy foods trigger yours, you can guess it is not allergic at all but simply Salmonella or Shigella infection. Boil all dairy foods, stop eating ice cream, cheese and yogurt which you cannot boil. If eating lettuce triggers your intestinal attack, but other roughage does not, it may be a true allergen and cleaning the liver will eventually cure it. Wheat “allergy” is due to the pancreas being full of pancreatic flukes, wood alcohol, Kojic acid (a mycotoxin), and gold. All these bowel diseases are quite easily cured by killing all parasites, bacteria, and viruses. Since reinfection is such a big problem, give your pet away until you are completely cured. For this reason, too, I recommend the Bowel Program (page 546) and Black Walnut Hull Tincture Extra Strength even though you may have gotten immediate relief from zapping alone. This is because sheep liver fluke and pancre- atic fluke are commonly the main parasites and these live in the pancreas and liver. Salmonella and Shigella are always part of the picture, too, as are various amoebae and fungi. The treatment is the same, kill all parasites and remove all pollutants, especially wood alcohol in commercial beverages. Reinfection is very quick too, if the rule about cooking dairy foods is not observed. Michelle Whorton had stomach pain at the middle of her abdomen, not related to eating. We found she had Ascaris (probably in her stomach where they cause indigestion and in- flammation). She was to be very careful with sanitation since they owned a number of farm dogs. Next seen after six weeks, she stated that all her previous problems were gone but she had a different pain in the mid-lower abdomen that got worse during her period and sent pain shooting down both legs. Her uterus was full of asbestos, arsenic, gold, silver, titanium, propyl alcohol, benzene, styrene, toluene and carbon tetrachloride. Mark Lippman, age 51, came in for his irritable bowel syndrome, hop- ing we would find Giardia and put an end to it quickly. He also had propyl alcohol built up in his body giving him a precancerous con- dition that needed immediate attention. The flukes were killed in twenty minutes, along with Ascaris (he had swollen eyelids). His young body also had a buildup of benzene, moth balls and carbon tetrachloride that he was eating, drinking, and breathing. His other problems recurred until he was older and could stop licking his fingers when eating. Tom Ochs, age 36, had chronic stomach problems, alternating consti- pation and diarrhea, was labeled “lactose intolerant” after an elaborate test, and finally had been diagnosed with irritable bowel syndrome. He was also toxic with cesium from drinking beverages out of clear plastic bottles. This frequently causes depression and he was happy to understand his mood changes. After changing to purer food and products and killing his parasites, he did not need to come back. Rex Callahan, age 5, had dark circles under his eyes, numerous ear infections until tonsils were removed and tubes put in, and many strep throat infections. We found he had sheep liver flukes and all their developmental stages in his blood and intestine. Nevertheless, in three months his bowel was nearly normal and the pain in his intestine much less. His parasites were quickly killed with a frequency gen- erator and he was put on the herbal parasite program. One month later his stomach felt much better, but he still had an occasional stomach ache. She had to be back on antibiotics and a few months ago the doctor began discussing tube implants with her since she was still on antibiotics (six months). Another ear, nose and throat doctor agreed with this opinion, but was willing to wait until Autumn. Our test showed pancreatic fluke infestation; this would easily lead to bad digestion, especially of milk and gluten in wheat. Simply killing the parasites (in both mother and baby) solved both problems and she did not need to come back. The ear infections were probably caused by bacteria and viruses brought in by the parasites. They all, including herself, had stomach problems, a lot of allergies, asthma, ear infections, and milk intolerance. His sister, Nola, had itching legs and headaches besides; she was toxic with bismuth and antimony (from shampoo fragrance and laundry fragrance). We found she had the three large flukes plus Chilomastix, dog whip worm, and amoebas in her intestine (but not in body organs). Her stomach and intestines were much too sensitive to accept parasite herbs, or in fact, anything— anything except slippery elm powder. Her blood test showed high phosphate levels since she was dissolving her bones to get cal- cium. By the 12th day of the parasite program she no longer needed colitis medicine; her bowel movements were down to twice a day, soft and formed, but still with a little blood streaking. She was able to eat fruits and vegetables but agreed to stay off wheat and corn until her liver was cleansed.