Isoptin

Isoptin 240mg

  • 30 pills - $41.58
  • 60 pills - $62.75
  • 90 pills - $83.92
  • 120 pills - $105.08
  • 180 pills - $147.42
  • 270 pills - $210.92
  • 360 pills - $274.43

Isoptin 120mg

  • 30 pills - $31.97
  • 60 pills - $46.15
  • 90 pills - $60.34
  • 120 pills - $74.52
  • 180 pills - $102.89
  • 270 pills - $145.44
  • 360 pills - $187.99

Isoptin 40mg

  • 60 pills - $34.29
  • 90 pills - $42.18
  • 120 pills - $50.06
  • 180 pills - $65.84
  • 270 pills - $89.50
  • 360 pills - $113.16

Ceruloplasmin is a copper-containing glycoprotein oxidase in plasma that converts ferrous iron to ferric iron blood pressure variation during the day buy discount isoptin 40 mg online, which then binds to transferrin blood pressure chart low to high order genuine isoptin line. In all cells there are mechanisms for metal ion homeostasis that frequently involve a balance between uptake and efflux systems. A large number of membrane-bound metal transport proteins have been discovered that transport metals across cell membranes Pharmacology of Metals Metals and metal compounds have a long and rich history of pharmacological use. Metallic agents, largely because of their potential toxicity, have been often used in chemotherapeutic settings. For instance, mercury was used in the treatment of syphilis as early as the 16th century. Today, many metallic chemicals remain valuable pharmacological tools in the treatment of human disease, as exemplified by the highly effective use of platinum compounds in cancer chemotherapy. In addition, inorganic arsenic has returned as a very effective chemotherapeutic and agent of choice against certain hematologic cancers. Other examples of medicinal metals used today include aluminum (antacids and buffered analgesics), bismuth (peptic ulcer), lithium (mania and bipolar disorders), and gold (arthritis). Metallic compounds find their way in to a variety of pharmacological preparations as active or inactive ingredients. Traditional Chinese medicines, usually complex mixtures, can be made with toxic metals, such as mercury, as intentional ingredients (Liu et al. Treatment of metal poisoning is sometimes used to prevent, or even attempt to reverse, toxicity. The therapeutic strategy is to give metal chelators that will complex the metal and enhance its excretion (Klaassen, 2006). Most chelators are not specific and will interact with a number of metals, eliminating more than the metal of concern. Metal chelation therapy should be considered a secondary alternative to toxic metal exposure reduction or even prevention. Chelator therapy can be used for many different metals including lead, mercury, iron, and arsenic. For detailed discussion on the pharmacology of chelation therapy, see Klaassen (2006). The word arsenic is from the Persian word Zarnikh, as translated to the Greek arsenikon, meaning "yellow orpiment. Arsenic exists in the trivalent and pentavalent forms and is widely distributed in nature. The most common inorganic trivalent arsenic compounds are arsenic trioxide and sodium arsenite, while common pentavalent inorganic compounds are sodium arsenate, arsenic pentoxide, and arsenic acid. Important organoarsenicals include arsanilic acid, arsenosugars, and several methylated forms produced as a consequence of inorganic arsenic biotransformation in various organisms, including humans. Occupational exposure to arsenic occurs in the manufacture of pesticides, herbicides, and other agricultural products. Arsenic compounds of low solubility (eg, arsenic trioxide, arsenic selenide, lead arsenide, and gallium arsenide) are absorbed less efficiently after oral exposure. Skin is a potential route of exposure to arsenic, and systemic toxicity has been reported in persons having dermal contact with solutions of inorganic arsenic (Hostynek et al. Deposition in airways and absorption of arsenicals from lungs is dependent on particle size and chemical form. The whole-body biological half-life of ingested arsenic is about 10 hours, and 50% to 80% is excreted over three days. Arsenic has a predilection for skin and is excreted by desquamation of skin and in sweat, particularly during periods of profuse sweating. Arsenic in the fingernails and hair has been used as a biomarker for exposure, including both current and past exposures, while urinary arsenic is a good indicator for current exposure. Methylation of inorganic arsenic species is no longer considered as a detoxication process, as recent work has identified the highly toxic trivalent methylated arsenicals (Drobna et al. Some animal species even lack arsenic methylation capacity, perhaps as an adaptation mechanism. Arsenate (As5+) is rapidly reduced to arsenite (As3+) by arsenate reductase (presumably purine nucleoside phosphorylase). However, large variations in arsenic methylation occur due to factors such as age and sex. Toxicity Acute Poisoning Ingestion of large doses (70­180 mg) of inorganic arsenic can be fatal. Symptoms of acute intoxication include fever, anorexia, hepatomegaly, melanosis, cardiac arrhythmia, and, 988 in fatal cases, terminal cardiac failure. Acute arsenic ingestion can damage mucous membranes of the gastrointestinal tract, causing irritation, vesicle formation, and even sloughing. Sensory loss in the peripheral nervous system is the most common neurological effect, appearing at one to two weeks after large doses and consisting of Wallerian degeneration of axons, a condition that is reversible if exposure is stopped. Anemia and leucopenia, particularly granulocytopenia, occur a few days following high-dose arsenic exposure and are reversible. Intravenous arsenic infusion at clinical doses in the treatment of acute promyelocytic leukemia may be significantly or even fatally toxic in susceptible patients, and a few sudden deaths have been reported (Westervelt et al. Arsine gas, generated by electrolytic or metallic reduction of arsenic in nonferrous metal production, is a potent hemolytic agent, producing acute symptoms of nausea, vomiting, shortness of breath, and headache accompanying the hemolytic reaction. The hematologic consequences of chronic exposure to arsenic may include interference with heme synthesis, with an increase in urinary porphyrin excretion, which has been proposed as a biomarker for arsenic exposure (Ng et al.

Isoptin dosages: 240 mg, 120 mg, 40 mg
Isoptin packs: 30 pills, 60 pills, 90 pills, 120 pills, 180 pills, 270 pills, 360 pills

Part of this is due to the difficultly in determining the energy expenditure amount heart attack 720p movie isoptin 120 mg order on line, because the energy expended by an individual on 30 minutes of physical activity differs according to body weight blood pressure medication yellow pill generic isoptin 40 mg without prescription, body composition, health, physical conditioning, and the activity itself (eg, walking, jogging at 4 miles/h, running a four-minute mile, or swimming a mile). In addition, overweight people are usually not accustomed to physical activity at the intensity level and duration needed to induce the body to burn body fat stores that lead to significant body fat reduction. This, when combined with the necessary changes in the diet composition and reductions in caloric intake, makes it difficult to lose body fat and more difficult to maintain a healthy body composition. Walking 30 minutes at a rate of 4 miles/h for the 160-lb man or woman described above will burn approximately 180 cal. So if an overweight individual were to maintain the same caloric intake (and same diet) and just increase his or her activity level to 30 minutes of walking at 4 miles/h (a total of 2 miles per day), the calculated fat loss would be 1 lb every 20 days. If he or she also reduced the caloric intake by 180 cal a day and has the same walk schedule, he or she would reduce the time to lose 1 lb of weight to about 10 days. Thus, the way to reduce body fat (adipose tissue) is to consume less calories than expended (energy deficit) and the rate of fat loss is directly related to the level of the energy deficit (ie, caloric intake vs caloric expenditure). There are several ways and several commercially available diet systems in which this can be accomplished. One of the most widely used diet systems, the Atkins diet, claims to accomplish this by increasing protein (and consequently fat) and limiting carbohydrates. Following a meal containing an abundance of simple carbohydrates, blood glucose levels rise and glucose gets converted in to glycogen by the liver and stored there for future energy use. As glucose enters cells, blood glucose concentrations would fall if not for the liver converting the glycogen back to glucose and releasing it back in to the blood. Use of glucose as the primary energy source seems to be prioritized by cell and organ type, with nerve cells having the highest priority. This means that if body glucose stores become scarce, the brain will be the last organ able to use glucose as its primary source. In this case, if another carbohydrate-containing meal is not consumed and blood glucose levels dropped to very low levels, lower priority organs (such as muscle) would need another source of energy and this source is fatty acids released from fat stores (lipolysis). Just like glycogen is the storage form for glucose, fat is the storage source for fatty acids and tissues can easily burn fatty acids when glucose is absent. As liver glycogen stores become minimal, amino acids are converted to glucose (gluconeogenesis). This can support nerve cell metabolism for a while, but eventually the brain will switch from burning pure glucose and start to utilize ketone bodies produced in the liver from fatty acids as an additional energy source. Under conditions of adequate carbohydrate intake, insulin causes excess sugar not utilized as fuel to be stored as fat and prevents utilization of fat as an energy source. Thus, a highcarbohydrate diet tends to induce insulin secretion, which promotes carbohydrate energy storage as fat and tends to reduce the utilization of fat as an energy source. In theory, the low carbohydrate, high protein intake promoted in the Atkins diet forces the body to burn more fat. This would call for the body to switch from using pure carbohydrates for fuel to using more fat for fuel and the source of this fat is the adipose tissue. Thus, when insulin levels are normal, the body will begin to burn its own fat as fuel, thereby resulting in body weight loss. Dieting as described in this chapter is based on the use of a healthy diet that meets the daily nutrient needs of the body, but at a reduced caloric intake and with increased moderate physical activity. The overarching premise is to provide adequate nutrients for normal cellular function, while reducing caloric intake to a level that forces the use of fat stores as an energy source to meet the energy expenditure above the caloric intake. If the diet does not include all the required nutrients (an imbalanced diet), metabolism will suffer and with time this can result in health problems. This is true whether in the case of deficiency of specific nutrients (deficiency disorders such as anemia or osteoporosis) or toxicity caused by excesses of a particular nutrient (such as thyroid impairment, vitamin deficiencies, mental confusion). Some popular diet plans call for excess intake of a particular food and these can not only alter metabolism but also interfere with medications. This may increase drug concentrations to toxic levels, increase drug­drug interactions, and result in potential health problems (Ameer and Weintraub, 1997; Kiani and Imam, 2007). Another potential adverse effect of dieting is known as the yo-yo effect or weight cycling. This is caused when a dieter starts one diet and loses a significant amount of body weight and body fat, but cannot maintain the diet and stops to return to the prediet routine. In fact, the yo-yo experience may actually result in a condition in which the dieter is more efficient in gaining weight. This results in the dieter selecting another diet plan, loss of weight, failure to maintain the diet, and return to overweight or obese conditions. There are often periods of depression and fatigue associated with this cycling behavior and the end results are extreme emotional and physical ramifications. Whether the yo-yo dieter has other health issues remains ill-defined and controversial. Drug Therapy for Weight Loss In addition to the diet plans described above, many overweight individuals turn to drug therapy to help lose body weight. Appetite suppressants, for example, sympathomimetics such as diethylpropion, attempt to lessen the psychological motivation for food, usually by acting on central nervous system appetite control centers, such as those in the hypothalamus (Guaraldi et al. Although sympathomimetics can be used for long periods of time, their appetite-reducing effects tend to decrease after a few weeks in many people. Thus, appetite suppressants are often used in the early stages of a weight loss program. People are likely to lose weight while taking sympathomimetics, but the weight loss is generally temporary without modifications in diet composition, eating behavior, and physical activity. Short-term use is usually accompanied by minor side effects such as thirst, irritability, constipation, stomach pain, dizziness, dryness of mouth, heightened sense of well-being, headache, irritability, nausea, nervousness or restlessness, trembling or shaking, and trouble sleeping. However, long-term use of appetite suppressants often times leads to more serious side effects: intracerebral hemorrhage, acute dystonia, myocardial injury, psychosis, cerebral arteritis, cardiac arrhythmias, heart valve damage, and even fatal pulmonary hypertension. These side effects have led to the withdrawal of several such products from the market.

Dwarf Pine Needle. Isoptin.

  • Dosing considerations for Dwarf Pine Needle.
  • What is Dwarf Pine Needle?
  • Are there safety concerns?
  • How does Dwarf Pine Needle work?
  • Preventing skin infections and clearing mucus from the lungs.

Source: http://www.rxlist.com/script/main/art.asp?articlekey=96439

Single cell necrosis heart attack 70 blockage isoptin 240 mg lowest price, evident five to six hours postdosing fetal arrhythmia 33 weeks purchase online isoptin, progresses to maximal centrilobular necrosis within 24 to 48 hours. A variety of cytoplasmic enzymes are released from dead and dying hepatocytes in to the bloodstream. The activity of these enzymes in serum generally parallels the extent of necrosis in the liver. Both unstable radicals bind covalently to a variety of cellular components including enzymatic and structural proteins and polyunsaturated fatty acids in membranes. This results in lipoperoxidation, loss of intracellular and cellular membrane integrity, and leakage of enzymes (Plaa, 2000; Weber et al. Increased cytosolic Ca2+ levels may result from influx of extracellular Ca2+ due to plasma membrane damage and from decreased intracellular Ca2+ sequestration. Elevation of intracellular Ca2+ in hepatocytes can cause activation of phospholipase A2 and exacerbation of membrane damage (Glende and Recknagel, 1992). Elevated Ca2+ may also be involved in alterations in calmodulin and phosphorylase activity, as well as changes in nuclear protein kinase C activity (Omura et al. High intracellular Ca2+ levels activate a number of catabolic enzymes including proteases, endonucleases, and phospholipases, which kill cells via apoptosis or necrosis (Weber et al. They were not found in hepatocytes of F344 rats, Syrian golden hamsters, or three human subjects (Casanova et al. These links were four-, seven-, and 14-fold higher in cells from mice than in cells from rats, humans, and hamsters, respectively. Clara cells are present in much lower numbers in rats, and are rare in human lungs. It also produces differential upregulation of multidrug resistance proteins that are involved in export of oxidative stress products and metabolites. This early phase regeneration (arrested G2 hepatocytes activated to proceed through mitosis) is followed at 24 hours by the secondary phase of regeneration (hepatocytes mobilized from Go/G1 to proceed through mitosis) (Bell et al. There have been extensive studies of its potential genotoxic and mutagenic effects, but the results are largely negative in bacterial and in mammalian systems. There was a significant increase in hepatocellular adenomas and carcinomas in the male and female rats at the highest exposure level. Significant increases in these tumors and in adrenal pheochromocytomas were manifest in the 25- and 125-ppm male and female mice. There was a statistically significant, but more modest elevation in hepatocellular adenomas, but not carcinomas, in the 5-ppm female mice. Degenerative and necrotic hepatic changes were seen in livers of all groups of animals with liver tumors except the 5-ppm female mice. Four weeks after cessation of this treatment, most gene expression profiles returned to control levels, except fibrogenesis. More recently, mice exposed daily for 7, 14, and 30 days were found to have a robust regenerative response in target tissues, which prevented the progression of injury (Anand et al. These studies have provided valuable insight in to the importance of both the timing of the tissue repair response and its magnitude as pivotal determinants of the outcome of toxicant-induced injury, emphasizing the need to consider repair processes in predictive toxicology (Anand et al. It causes liver and kidney tumors that are species-, strain-, sex-, and route of exposure­dependent. These same authors observed that male but not female mice suffered kidney necrosis. Such binding damages membranes and other intracellular structures, leading to necrosis and subsequent reparative cellular proliferation. In doing so, the Agency concluded that the RfD for noncancer effects, based on the dog study of Heywood et al. They concluded that no safety factor was needed to account for interspecies differences in inhalation cancer risk. Inhalation is the primary route of exposure in industrial and in everyday settings. Benzene is present in the atmosphere both from natural sources such as forest fires and oil seeps and from industrial uses including automobile exhaust and gasoline vapor emission. Smokers have benzene body burdens that are six to 10 times greater than those of nonsmokers. Because of the health risks of benzene exposure, the use and environmental release of this chemical has significantly diminished in the last two decades. Evidence of increased risks of other cancers in such populations is less compelling. Marginal, nonsignificant increases were seen for lung cancer and chronic myelogenous leukemia. Some investigations of persons exposed to engine exhausts have reported a significant association with multiple myeloma. Increased incidences of malignant lymphomas and a variety of solid tumors were found in male and female B6C3F1 mice dosed orally with high doses of benzene for up to 103 weeks (Huff et al. Asterisks (*) denote a significant difference from similarly treated control mice (<0. Such a mechanism would still be threshold dependent, given its reliance on the initial depletion of antioxidants. Thus, benzene is clearly an animal and human carcinogen, but major species differences exist. The most important adverse effect of benzene is hematopoietic toxicity, which precedes leukemia.

Syndromes

  • Irritability
  • Coronary artery bypass (CABG) surgery or angioplasty can improve blood flow to the damaged or weakened heart muscle.
  • Enlarged prostate, straining to urinate
  • Toluene (methylbenzene, phenylmethane)
  • Abnormal fluid buildup in the covering of the heart due to bacterial or viral infection or surgical complications
  • Bronchoscopy -- camera down the throat to see burns in the airways and lungs
  • Diving accident

Because of the potential for renal toxicity blood pressure medication dizzy order isoptin 240 mg mastercard, there is considerable concern about the levels of dietary cadmium intake for the general population blood pressure of 150 100 isoptin 120 mg purchase on-line. In fact, it is thought that upwards of 7% of the general population may have significant cadmium-induced kidney alterations due to chronic exposure with kidney cadmium levels as low as 50 µg/g (Järup et al. Cadmium-induced renal toxicity is reflected by proteinuria as a result of renal tubular dysfunction. The presence of larger proteins, such as albumin and transferrin, in the urine after occupational cadmium exposure suggests a glomerular effect as well. The pathogenesis of the glomerular lesion in cadmium nephropathy is not well understood (Prozialeck and Edwards, 2010). Urinary excretions of proteins and cadmium have been used as biomarkers for cadmium exposure. Nephrotoxicity in normal rats following liver transplantation from cadmium-exposed rats supported this hypothesis (Chan et al. It is likely that inorganic cadmium can bind to other lowmolecular-weight proteins or other complexes for renal uptake, and these complexes can contribute to chronic cadmium nephropathy (Zalpus and Ahmad, 2003). Chronic Pulmonary Disease Cadmium inhalation is toxic to the respiratory system in a fashion related to the dose and duration of exposure. Cadmium-induced obstructive lung disease in humans can be slow in onset, and results from chronic bronchitis, progressive fibrosis of the lower airways, and accompanying alveolar damage leading to emphysema. Pulmonary function is reduced with dyspnea, reduced vital capacity, and increased residual volume. The chronic effects of cadmium on the lung clearly increased the mortality of cadmium workers with high exposure. The long-term consumption of cadmiumcontaminated rice caused Itai-Itai disease, which occurred mostly in multiparous elderly women and was characterized by severe osteomalacia and osteoporosis, resulting in bone deformities and concomitant renal dysfunction. Vitamin D deficiency and perhaps other nutritional deficiencies are thought to be cofactors in Itai-Itai disease. Issues with loss of bone density, height loss, and increased bone fractures have now been reported in populations exposed to far lower levels of environmental cadmium than Itai-Itai victims (Kazantzis, 2004). Cadmium affects calcium metabolism, at least partially through renal dysfunction, and excess excretion of calcium often occurs in the urine. The skeletal changes are possibly related to a loss or decrease of calcium absorption, and interference with the actions of parathyroid hormone, disruption of collagen metabolism, and impairment of vitamin D activity (Nordberg et al. Cadmium may also act directly on bone and animal studies have shown the metal stimulates osteoclast activity, resulting in the breakdown of bone matrix. Cadmium in bone interferes with calcification and bone remodeling (Wang and Bhattacharyya, 1993). In accord with human victims of Itai-Itai, multiparity in mice enhances the osteotoxicity of cadmium (Bhattacharyya et al. Cardiovascular Effects Some epidemiological evidence suggests cadmium may be an etiologic agent for cardiovascular disease including hypertension, although these associations are not observed in all studies (Järup et al. Neurotoxicity There are only limited data from animals and humans that cadmium can be neurotoxic (Järup et al. Studies in humans have suggested a relationship between abnormal behavior and decreased intelligence in children and adults exposed to cadmium, but are typically complicated by exposure to other toxic metals. Furthermore, the blood­brain barrier severely limits cadmium access to the central nervous system, and a direct toxic effect appears to occur only with cadmium exposure prior to blood­brain barrier formation (young children), or with blood­brain barrier dysfunction under certain pathological conditions. Additionally, the choroid plexus epithelium may accumulate high levels of cadmium reducing access to other areas (Zheng, 2001). Lung tumors can also be produced by systemic cadmium exposure in mice (Waalkes, 2003). Beyond the lung, in rodents cadmium can produce a variety of tumors, including malignant tumors at the site of repository injection (subcutaneous, etc). Compounds such as cadmium chloride, oxide, sulfate, sulfide, and cadmium powder produce local sarcomas in rodents after subcutaneous or intramuscular injections. A single injection can be effective, but multiple injections of cadmium at the same site cause more aggressive sarcomas that show a higher rate of local invasion and distant metastasis. Cadmium also induces tumors of the testes, specifically benign Leydig cell tumors, but this is likely due to a high-dose mechanism involving acute testicular necrosis, degenerative testicular atrophy, and subsequent overstimulation by luteinizing hormone, factors very likely of limited relevance in humans (Waalkes, 2003). Other studies have found that cadmium exposure can induce tumors of the pancreas, adrenals, liver, kidney, pituitary, and hematopoietic system in mice, rats, or hamsters. Cadmium can be carcinogenic in animals after inhalation or oral administration or by various injection routes (Waalkes, 2003). Emerging evidence indicates that cadmium exposure significantly increases the risk of breast and endometrial cancers (McElroy et al. Cadmium appears to also work through estrogenic and nonestrogenic mechanisms in hormone-related cancers (Akesson et al. In certain cases (Itai-Itai disease, osteomalacia) vitamin D is prescribed, although its effects have not been satisfactory (Nordberg et al. In experimental systems some chelators can reduce acute cadmium-induced mortality (Klaassen et al. Chromium Chromium (Cr) was named from the Greek word "chroma" meaning color, because of the many colorful compounds made from it. It is part of the mineral crocoite (lead chromate), and the element was first isolated in 1798. Most naturally occurring chromium is found in the trivalent state in chromite ores, which are generally refined to ferrochromium or metallic chromium for use in industrial processes. Because trivalent chromium (Cr3+) is an essential trace nutrient important for glucose metabolism, it will be discussed separately in the section "Essential Metals with Potential for Toxicity.

Usage: p.c.

Lipophilic solvents also partition in to phospholipids hypertension with bradycardia isoptin 240 mg, 1038 lipoproteins blood pressure bottom number is high order isoptin 240 mg mastercard, and cholesterol present in the blood. The brain is an example of a rapidly perfused tissue with a relatively high lipid content. Lipophilic solvents therefore quickly accumulate in the brain after the initiation of exposures (Warren et al. Route of exposure can significantly influence target organ deposition and toxicity of solvents. Much of the pre-1980s toxicology database for solvents comprised results of inhalation studies. Such a practice is obviously not scientifically valid, when physiological differences in the absorption pathways are taken in to account. For convenience, test chemicals are typically given daily to animals as a single bolus by gavage in short- and long-term oral toxicity and carcinogenicity studies. Actual human exposures to solvents in drinking water are quite different, in that people typically ingest water in divided doses. No evidence of hepatic tumorigenesis was seen, however, when these mice were given the same doses of the chemical in their drinking water (Jorgenson et al. Oral bolus doses of solvents can cause damage of extrahepatic organs by exceeding the capacity of hepatic and pulmonary first-pass elimination, as well as protection and repair processes of hepatocytes. Rats inhaled 45 mg/L of toluene or acetone for 20 minutes or three hours, respectively. This can be attributed to redistribution of toluene from the brain to body fat and other tissues, as well as to relatively rapid metabolism and exhalation. In contrast, recovery from acetone narcosis does not occur for at least nine hours postexposure. It is instead distributed in the considerable volume of the blood and other body water. Clearance of acetone is slow due to its large volume of distribution and its relatively slow metabolism and exhalation. Blood concentrations of such solvents drop very rapidly during the initial elimination phase following cessation of exposure. This so-called redistribution phase is characterized by rapid diffusion of solvents from the blood in to tissues. Equilibration of adipose tissue is prolonged due to the small fraction of cardiac output (3%) supplying fat depots. Body fat increases the volume of distribution and total body burden of lipophilic solvents. Rats with excess body fat experienced leukopenia during chronic benzene exposure, whereas their thinner counterparts did not. Metabolism Biotransformation plays a key role in modulating the toxicities of many solvents. Certain cellular enzymes can convert them to relatively water-soluble derivatives, which may be more readily eliminated in the largely aqueous urine and/or bile. Conversion of a bioactive parent compound to a less bioactive or inactive metabolite(s) that is(are) efficiently eliminated is termed metabolic inactivation, or detoxification. Toluene, Elimination the rate of systemic elimination of different solvents varies considerably. It is metabolized to hydroxyl and carboxyl metabolites, which are too polar to accumulate or remain in substantial quantities in neuronal membranes. Metabolism of other solvents can produce reactive metabolites that are cytotoxic and/ or mutagenic. Benzene, for example, is oxidized to a variety of epoxides, quinones, and semiquinones that can produce hematopoietic toxicities and leukemia (Snyder, 2004). Some of these competing pathways are considered bioactivation, others detoxification pathways. A variety of factors can influence the prominence of the different pathways and hence alter toxicity outcomes. Xenobiotic metabolism under physiological conditions may favor one or two isoforms as the primary catalysts for a given chemical. Inheritable gene alterations, such as base changes and deletions, can result not only in functionally deficient enzymes but also in the absence of certain P450s (Ma et al. It is found predominantly in liver, with lower levels present in kidneys, lungs, brain, testes, and other extrahepatic tissues of rodents and humans. These compounds are oxidized to electrophilic metabolites, capable of causing cytotoxicity and/or mutagenicity (Raucy et al. Activity of the isoform varies from species to species and from human to human (Snawder and Lipscomb, 2000). Starving rats, however, apparently must engage in coprophagy for induction to occur (Chung et al. A variety of environmental factors can predispose people to harmful effects of solvents by altering P450s (Lof and Johanson, 1998). The person who drinks in such a manner may be subject to potentiation of solvent toxicity, due to increased solvent metabolic activation (Manno et al. Conversely, ethanol consumed at about the same time as a solvent exposure can be protective by competitively inhibiting metabolic activation of the solvent. As capacity-limited (ie, metabolic capacity of the liver) metabolism prevails for poorly metabolized solvents, irrespective of dose, induction of their metabolism could be toxicologically significant in high (occupational) or low (environmental) exposure settings. In contrast, alterations of the bioactivation of low doses of well-metabolized solvents should be of little consequence, as their biotransformation is perfusion (ie, hepatic blood flow) limited. Under such circumstances, interindividual metabolic differences should have little influence on cancer risks posed by trace levels of such solvents.

References

  • Andrew M, David M, Adams M, et al. venous thromboembolic complication (VTE) in children. An analysis of the Canadian registry of VTE. Blood. 1994;83:1251-7.
  • Paranjothi S, Yusen RD, Kraus MD, et al. Lymphoproliferative disease after lung transplantation: comparison of presentation and outcome of early and late cases. J Heart Lung Transplant. 2001; 20(10):1054-1063.
  • Bayas A, Gold R, Naumann M. Long-term treatment of Lewis-Sumner syndrome with subcutaneous immunoglobulin infusions. J Neurol Sci. 2013;324:53-56.
  • Munnich A, Saudubray JM, Taylor J, et al. Congenital lactic acidosis alpha-ketoglutaric aciduria and variant form of maple syrup urine disease due to a single enzyme defect: dihydrolipoyl dehydrogenase deficiency. Acta Paediatr Scand 1982;71:167.