Vitamin C is excreted primarily in the urine medicine youth lyrics discount thorazine 100mg, and urinary excretion increases with increasing vitamin C intake medicine q10 order thorazine 100mg with visa. To support this argument treatment 2 go trusted thorazine 50 mg, Stone pointed out that humans are among a small group of species (including monkeys medications ranitidine order thorazine 50 mg online, guinea pigs medications hypothyroidism buy cheap thorazine 50mg on line, and an Indian fruit-eating bat) that are unable to synthesize vitamin C medications 3 times a day generic 50mg thorazine visa. While the human liver contains the first 3 of the 4 enzymes involved in the biosynthesis of vitamin C from glucose, the fourth enzyme (L-gulonolactone oxidase) is missing or defective. Stone named this genetic defect hypoascorbemia, in reference to the abnormally low levels of vitamin C that can exist in species that are unable to synthesize vitamin C. He hypothesized that "full correction" of this inborn error of metabolism would require supplying the individual with as much vitamin C as the liver would be synthesizing if the genetic defect were not present. Among animals that synthesize vitamin C, the amounts produced per 70 kg of body weight per day are 1. Itispossiblethatsomebenefitcanbederived from having the blood and tissues saturated with vitamin C and from large amounts of the vitamin being excreted in the urine and sweat. For example, because vitamin C has antiviral and antibacterial activity, excretion of large amounts in the urine and sweat might help prevent urinary tract and cutaneous infections. It might seem counterintuitive that mutants unable to synthesize vitamin C would have a survival advantage over those who were capable of synthesizing the vitamin. However, studies in bacteria have shown that, in the presence of an ample supply of a particular essential nutrient, a mutant that is unable to synthesize the nutrient will win the competition for survival against the wild type that is capable of synthesizing the nutrient. In this ascorbate-rich prehistoric metaphorical Garden of Eden, the loss of the capacity to synthesize vitamin C may indeed have been a survival advantage. In reality, full correction of defective vitamin C biosynthesis is not possible, because one cannot duplicate with oral supplementation the steady release of large amounts of vitamin C from the liver into the bloodstream. As compared with maximum hepatic synthesis and release of vitamin Deficiency ManifestationsofseverevitaminCdeficiency(scurvy)may include bleeding abnormalities (petechiae, perifollicular and subperiosteal hemorrhage, ecchymoses, purpura, bleeding gums, and hemarthrosis), bone pain, osteoporosis, arthralgias, myalgias, edema, ascites, orthostatic hypotension, parkinsoniansymptoms(combinedvitaminCandzincdeficiency), cardiomegaly, and electrocardiographic abnormalities suggestive of cardiac disease. These events occurred in the absence of overt signs of scurvy, and were similar to the observations of James Lind (a pioneer in the treatment of scurvy), who wrote in 1757, "Persons that appear to be but slightly scorbutic are apt to be suddenly and unexpectedly seized with some of its worse symptoms. Their dropping down dead upon an exertion of their strength, or change of air, is not easily foretold. Nevertheless, the concept of hypoascorbemia as a genetic defect provides a theoretical framework to support the clinical observations of many practitioners that megadoses of vitamin C are useful for preventing and treating a wide range of health conditions. Researchers skeptical of the value of high-dose vitamin C have pointed out that when vitamin C intake is high, further increases in intake produce only small increases in plasma or tissue levels of the vitamin. For example, increasing vitamin C intake from 200 mg/day to 2,500 mg/day raised the mean plasma vitamin C level by only 25%. Furthermore, vitamin C might have positive effects that are unrelated to an increase in plasma or tissue levels of the vitamin. It has been suggested that high intake of vitamin C induces the formation of enzymes that promote the metabolism of vitamin C to other compounds, some of which may bebeneficial. Forexample,oxidationproductsofvitaminC were found to have a greater anticancer effect in mice than vitamin C itself. In addition, serum vitamin C levels decline in response to inflammation, and serum vitamin C may be an unreliable indicator of vitamin C status when the C-reactive protein level is 5 mg/L or higher. These symptoms are dose-related and can be reduced or eliminated by decreasing the total daily dose, taking vitamin C in several divided doses throughout the day, taking the vitamin with food, or using buffered forms of vitamin C. It has frequently been claimed that ingestion of large doses of vitamin C can increase the risk of calcium oxalate kidney stones, because vitamin C is converted in part to oxalate. However, the hyperoxaluria associated with use of high-dose vitamin C has been found to be due primarily to a laboratory artifact, resulting from the conversion of vitamin C to oxalate ex vivo. If there is a small increase in urinary oxalate resulting from ingestion of large doses of vitamin C, that increase might be counterbalanced by other effects of the vitamin. For example, vitamin C binds calcium in the urine, potentially reducing the formation of calcium oxalate crystals; produces a small increase in urinary acidity, thereby increasing calcium oxalate solubility; and possibly decreases urinary stasis by promoting diuresis. Observational studies have not provided any clear evidence that high vitamin C intake increases the risk of kidney stones. Moreover, practitioners who have routinely used large doses of vitamin C have not observed kidney stones as a side effect. Despite the apparent safety of vitamin C for the general population with respect to kidney stone risk, there are rare cases in which high-dose vitamin C appeared to cause a substantial increase in urinary oxalate levels. For example, a 25-year-old male with no history of kidney stones had a 350% increase in urinary oxalate excretion (which manifested as hematuria) while ingesting 8 g/day of vitamin C. In addition, even moderate doses of vitamin C have the potential to cause oxalosis in people who have risk factors for oxalosis (such as prior gastric bypass surgery and chronic kidney disease). Children less than 1 year of age,23 the elderly (particularly those living in nursing homes), cigarette smokers, and lowincome individuals are at increased risk of having low vitaminCstatus. Peoplewithgastroesophagealrefluxmayalso besusceptibletodevelopingvitaminCdeficiencybecauseof an aversion to acidic foods that are rich in vitamin C. Treatment with high-dose vitamin C has been associated with acute renal failure (apparently secondary to the deposition of calcium oxalate crystals) in patients with preexisting renal disease. One patient, who had nephrotic syndrome and renal amyloidosis, developed acute renal failure after intravenous administration of 45 g of vitamin C. As noted in chapter 204, even modest doses of vitamin C (such as 500 mg/ day orally) can cause hyperoxalemia in patients with end-stage renal disease. Other reports of vitamin C adversely affecting renal function are less convincing. A 22-year-old woman with extensive small-bowel resection who required home parenteral nutrition developed hyperoxaluria and an elevated serum creatinine level while receiving 1. In another case report, a 31-year-old male developed acute renal failure secondary to acute tubular necrosis after taking 5 g/day of vitamin C for an upper respiratory tract infection. Among the many thousands of patients who have received this treatment, there have been no reports of severe hemolytic episodes. Therefore,itremainsuncertainwhenoraladministration of vitamin C can cause hemolysis. When guinea pigs were given large doses of vitamin C and then put on a scorbutic diet, the scurvy was more severe than in guinea pigs fed the scorbuticdietwithoutfirstgivingthemlargedosesofvitaminC. It would therefore be prudent for individuals taking large amounts of vitamin C who decide to reduce their dosage to do so gradually. One practitioner stated that patients taking high maintenance doses of vitamin C should not be deprived of the vitamin during emergency hospitalizations, and that they should have a Medic Alert type bracelet describing their increased vitamin C requirement. The author of this report suggested that the use of these "large doses" of vitamin C may have resulted in rebound scurvy in the infants. First, while Cochrane did not mention how old his 2 patients were when they developed scurvy, an evaluation of Iron overload. Because vitamin C increases the absorption of nonheme iron, vitamin C supplementation could worsen iron overload in patients with increased body iron stores. Vitamin C may also increase iron-induced oxidative damage in patients with iron overload. One patient received a single 80-g infusion and the other patient received 80 g on 2 consecutive days. If the infants described by Cochrane truly had "rebound scurvy," one would have expected them to become ill shortly after they were born, not many months later. Second, millions of women have consumed more than 400 mg/day of vitamin C during pregnancy (through diet and supplements) since 1965. Moreover, one practitioner who prescribed large doses of vitamin C to thousands of patients over a 23-year period did not see any cases of scurvy in the infants of mothers who took vitamin C during pregnancy. Conscientious mothers, concerned about the dangers of germs for their baby, would in some cases re-boil even the sterilized milk they had purchased, just to "make quite sure. Infantile scurvy was an important public-health problem in Canada in the 1950s and 1960s, largely because many parents were feeding their infants nothing but evaporated milk, which is deficient in vitamin C. Some pediatricians recommended liquid vitamin C supplements, but these supplements were apparently added to the reconstituted milk, which may have then been boiled prior to giving it to the infant. Thus, there is no convincing evidence that maintaining high vitamin C intake during pregnancy is detrimental to the infant. Some, but not all, studies have found that vitamin C supplementation increases urinary excretion of uric acid and lowers serum uric acid levels (chapter 151). It has been hypothesized that vitamin C, like other uricosuric agents, could precipitate gout attacks in susceptible individuals by causing rapid migration of uric acid from the tissues. However, practitioners who have administered large doses of vitamin C to thousands of patients to treat various medical conditions have not encountered any cases of vitamin Cinduced gout. In addition, a 20-year prospective study found that higher intake of vitamin C from food and supplements was associated with a lower incidence of gout. To obviate the theoretical concern that vitamin C could trigger a gout attack, when considering the use of high-dose vitamin C for a patient with a history of gout, it would be reasonable to begin with relatively modest doses and build up gradually. Chewing ascorbic acid tablets or otherwise allowing ascorbic acid to have direct contact with the teeth can result in erosion of dental enamel. In addition, the teeth should be rinsed after ingestion of ascorbic acid crystals or powder. While one might expect that buffered forms of vitamin C would not erode dental enamel, there has not apparently been any research addressing that issue. There is one case report of tumor necrosis, hemorrhage, and subsequent death occurring in a cancer patient after a single intravenous dose of 10 g of vitamin C. Further information and precautions related to the use of high-dose vitamin C in cancer patients is presented in chapter 325. Adverse effects and precautions regarding intravenous administration of vitamin C are discussed above, and additional information is provided in chapter 341. Drug interactions Note: References for some of the information below are provided in chapter 342. Co-administration of 2 g of vitamin C and aluminum hydroxide (an antacid), as compared with administration of aluminum hydroxide by itself, increased urinary excretion of aluminum, presumably because of an increase in intestinal aluminum absorption. In rats given aluminum hydroxide, co-administration of vitamin C increased the concentration of aluminum in liver, brain, and bone. These observations raise the possibility that vitamin C increases the absorption of other forms of aluminum as well. Interactions between vitamin C and anesthetic agents are discussed in chapter 336. Administration of vitamin C (500 mg twice a day) to a man with low vitamin C levels who wasreceivingtheneurolepticdrug,fluphenazine,forbipolar disorderresultedina25%decreaseinplasmafluphenazine levels and a deterioration of his clinical condition. In case reports, supplementation with vitamin C (2 g 3 times per day) appeared to reverse amenorrhea and irregular menses associated with neuroleptic use. Aspirin has been reported to increase urinary excretion of vitamin C and to decrease platelet vitamin C concentrations. Vitamin C supplementation may therefore be beneficialforpeopleonlong-ermaspirintherapy. Some, but not all, studies found that the use of oral contraceptives decreased plasma vitamin C levels. In guinea pigs, administration of vitamin C prevented the development of doxorubicin (Adriamycin)induced cardiomyopathy. Vitamin C had no effect on the antitumor activity of doxorubicin in mice with experimentally induced tumors (chapter 325). In patients receiving large doses of glucocorticoids, administration of 2 g/day of vitamin C corrected glucocorticoid-induced defects in polymorphonuclear neutrophil function, an effect that might help prevent the increase in susceptibility to infections associated with long-term glucocorticoid use. Treatment with interleukin-2 has been reported to cause a marked decrease in plasma vitamin C levels. In one study, plasma vitamin C fell by 80% after the firstphaseoftreatmentandbecameundetectablein8of11 patients as treatment progressed (chapter 325). The effect of vitamin C supplementation on the anticancer effect of interleukin-2 has not been investigated. In a case report, supplementation with vitamin C appearedtoenhancetheefficacyoflevodopa(chapter139). In patients with a history of gastritis, ingestion of 500 mg of vitamin C along with levothyroxine appeared to increase the bioavailability of the drug. Interactions between vitamin C and opioid narcotics, and the use of vitamin C to treat opioid addiction, are discussed in chapter 276. In healthy volunteers, administration of 2 g of vitamin C 30 minutes before a dose of propranolol significantly reduced the bioavailability of the drug. This effect appeared to be due to a combination of decreased drug absorption and an alteration in drug metabolism. Treatment with proton pump inhibitors decreased plasma vitamin C levels in healthy volunteers. Administration of 500 mg of vitamin C along with 250 mg of tetracycline increased the blood level of tetracycline after 2 hours by 3- to 15-fold, compared with the level after administration of tetracycline alone. In case reports, 2 patients had an increase in their warfarin requirement while taking vitamin C (16 g/day in one case,dosenotspecifiedintheothercase). In5otherpatients, administration of 1 g/day of vitamin C for 2 weeks had no effect on warfarin requirements. In animals, administration of vitamin C in doses up to 500 mg/kg of body weight per day did not alter the anticoagulant effect of warfarin. The case reports suggesting an interaction between vitamin C and warfarinmayhavebeenduetorandomfluctuationsincoagulation parameters, rather than to an effect of vitamin C. However, the possibility that large doses of vitamin C interfere with warfarin cannot be ruled out.
Malabsorption can be caused by intestinal bacteria that usurp vitamin B12 treatment plans for substance abuse buy discount thorazine 50mg on-line, achlorhydria medicine 2632 generic 100mg thorazine free shipping, pancreatic insufficiency symptoms 4 days after conception buy cheap thorazine 50 mg online, inadequate disassociation of vitamin B12 from proteins treatment canker sore purchase 100 mg thorazine amex, or lack of intrinsic factor receptors secondary to ileal loops medications 5 rs cheap thorazine 100mg with amex, bypass medications medicare covers order thorazine 100 mg otc, or surgical resection. He also complains of a painful tongue, alternating constipation and diarrhea, and a tingling sensation in both feet. Perti- nent findings on physical examination include pallor, red tongue, vibratory sense loss in the lower extremities, disorientation, muscle weakness, and ataxia. What signs, symptoms, and laboratory findings are typical of pernicious anemia in C. This disease occurs equally in both sexes (primarily in individuals of northern European descent), with an average onset of 60 years. Pernicious anemia develops from a lack of gastric intrinsic factor production, which causes vitamin B12 malabsorption and, ultimately, vitamin B12 deficiency. The presence of poikilocytosis and anisocytosis observed in the blood smear represent ineffective erythropoiesis. Erythroid hypercellularity, along with a decrease in the myeloid cells (leukocytes and platelets), increases the erythroid:myeloid ratio in C. A monthly maintenance dose of cyanocobalamin (100 mcg) would then be required for the remainder of C. Another treatment option may be cyanocobalamin (1,000 mcg) once a week for 4 to 6 weeks followed by 1,000 mcg/mo for lifetime maintenance therapy. An oral or intranasal cyanocobalamin gel is also available for maintenance therapy, after the patient has achieved hematologic remission. With adequate vitamin B12 therapy, the following response can be expected: Neurologic symptoms should improve within 24 hours. However, with longstanding vitamin B12 deficiency, several months may pass before some symptoms are relieved; other symptoms may never resolve. The bone marrow becomes normoblastic within 48 hours, the reticulocyte count should peak around day 5 of therapy, and the Hct should return to normal in 1 to 2 months. Peripheral blood counts should be obtained every 3 to 6 months to evaluate the adequacy of therapy. If maintenance therapy is discontinued, pernicious anemia will recur within 5 years. Today, she comes to the emergency department with a 4-week history of frequent (three to five per day) stools containing bright red blood. She reports continued lethargy, dizziness, ataxia, and paresthesias in her hands and feet. A subsequent bone marrow aspirate demonstrates megaloblastic erythropoiesis, giant metamyelocytes, and a low stainable iron. A barium swallow and follow-through show numerous jejunal and duodenal diverticuli. What signs, symptoms, and laboratory findings are typical for vitamin B12 deficiency in P. About 50% of a 1 to 2 mcg dose of vitamin B12 is absorbed, whereas only about 5% of a 20 mcg dose is absorbed. Oral therapy for pernicious anemia using high dosages of oral cyanocobalamin (1,000 to 2,000 mcg) may be indicated in certain patients, especially those who refuse or cannot receive parenteral therapy. Patients receiving oral vitamin B12 therapy should be monitored more frequently to ensure compliance with therapy. What form(s) of anemia would be expected to develop in a patient after gastrectomy? For example, her lethargy may be the result of prolonged blood loss secondary to diverticulitis. The presence of megaloblastic erythropoiesis and giant metamyelocytes in the bone marrow also is consistent with vitamin B12 deficiency. Partial or total gastrectomy often results in anemia, particularly pernicious anemia, because the source of intrinsic factor is lost, and oral vitamin B12 absorption will be impaired. The hematologic and neurologic abnormalities associated with B12 deficiency do not develop until existing vitamin B12 stores are depleted (about 2 to 3 years). Nevertheless, prophylactic vitamin B12 should be administered to this patient after total gastrectomy. Because the vitamin B12 stores are not currently depleted, maintenance therapy, as discussed in Question 12, should be adequate for F. The presence of diverticuli is not the cause of vitamin B12 malabsorption because diverticuli typically do not extend into the distal ileum. Folic Acid Deficiency Anemia Folic Acid Metabolism Folate is abundant in virtually all food sources, especially fresh green vegetables, fruits, yeast, and animal protein. As a result of food fortification, the average American diet provides 50 to 2,000 mcg of folate per day; however, excessive or prolonged cooking (>15 minutes) in large quantities of water destroys a high percentage of the folate that is contained in food. Folate requirements are increased in conditions in which the metabolic rate and rate of cellular division are increased. The following are estimates of daily folate requirements based on age and growth demands: children, 80 mcg; infants, 65 mcg; pregnant or lactating women, 400 to 800 mcg. Therefore, deficiency and subsequent megaloblastic anemia can occur within 3 to 4 months of decreased folate intake. Predisposing Factors Folate deficiency is most commonly associated with alcoholism, rapid cell turnover, and dietary deficiency. In alcoholics, the daily intake of the folate contained in food may be restricted or absent. In addition, enterohepatic recirculation of folate can become impaired by the toxic effect of alcohol on hepatic cells. Folate deficiency also can develop during the third trimester of pregnancy as a result of a marginal diet and the rapid metabolism of the fetus. Therefore, folate deficiency will develop in any condition of rapid cellular turnover. Folate deficiency also can occur with chronic hemodialysis, diseases that impair absorption from the small intestine. Large doses of folate can partially reverse hematologic abnormalities caused by vitamin B12 deficiency; however, folate cannot correct neurologic damage caused by vitamin B12 deficiency. Therefore, folate deficiency absolutely must be differentiated from vitamin B12 deficiency before folate therapy is initiated. Otherwise, the progression of the neurologic sequelae of vitamin B12 deficiency can occur. The diagnosis of folate deficiency is plausible, considering folate deficiency can develop in a matter of weeks to months. Cocaine and alcohol, together with multiparity complicated by anorexia, nausea, and vomiting, could lead to poor nutrition. Alcohol has toxic effects on the intestinal mucosa and interferes with folate utilization by the bone marrow. She may have a folate-poor diet for financial reasons or because she is overcooking her food. Serum folate concentrations generally reflect folate balance over the past 3 weeks, although one balanced meal can raise serum levels and falsely elevate body stores. Because the estimated total body folate store is only about 5 to 10 mcg, 1 mcg of folic acid given daily for 2 to 3 weeks should be more than adequate to replace her storage pool of folate. Higher dosages (up to 5 mcg) may be needed, however, if absorption is compromised by alcohol or other factors. She should be reassessed after the course of therapy to determine response to therapy and if the cause of the folate deficiency has been corrected. Supplementation with folic acid 1 mcg/day may be required as long as risk factors are present. If patients with underlying vitamin B12 deficiency are inappropriately treated with folate, neurologic sequelae will persist, and macrocytic anemia will abate but will not resolve completely. Hemoglobin is a quaternary structure composed of two -globin chains and two -globin chains (2 2) in adults. The -globin gene locus encodes several globin gene products during the course of development. During fetal development, the -globin is the primary -globin expressed, forming fetal hemoglobin (HbF or 2 2). Normally, the period from birth to approximately 3 to 6 months of age is marked by the replacement of -globin with -globin, giving rise to the adult form of hemoglobin (HbA, 2 2). Low levels of -globin persist throughout life, and HbF, present in F cells, may account for approximately 1% of the total hemoglobin content. Abnormal interactions with other cell types produce several complications such as anemia, vaso-occlusive episodes, and multiorgan damage. Patients with sickle cell anemia are homozygous, inheriting a sickle gene from each parent (2 S 2), whereas patients with sickle cell trait are heterozygous and have inherited the sickle cell gene from one parent and the HbA gene from the other parent (2 A S). Other inheritance patterns include patients with a sickle cell gene and an HbC gene (where glutamic acid is substituted for lysine B6 [2 S C]). Finally, patients may inherit the sickle cell gene and the -thalassemic gene (2 S Sthal), in which case the clinical course is less severe than with patients diagnosed with sickle cell anemia. During pregnancy, an increased frequency of urinary tract infections and hematuria are seen. If they do occur, they usually are caused by hypoxic conditions resulting from excessive exercise or high altitudes. These patients may have normal physical examination findings with only splenomegaly. Patients are at risk for bacterial infections and, because of elevated Hgb levels, they may suffer from ocular, orthopedic, and pulmonary vaso-occlusive events. The clinical course among patients with sickle cell disease is variable and difficult to predict. Organs such as the kidneys, retina, spleen, and bones are frequent sites of vaso-occlusive events because these sites have a relatively low pH and oxygen tension. The management of these complications is organ specific and aimed at supportive interventions. Erythropoietin response is typically blunted for the degree of anemia, which can be a result of concurrent kidney dysfunction. Some patients may even experience aplastic anemia (bone marrow failure) when extensive hemolysis is accompanied by inadequate bone marrow response. Management of the underlying anemia may include splenectomy following the first splenic sequestration event. Also, impaired splenic function increases the risk for infection from polysaccharide-encapsulated bacteria such as Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, and Salmonella typhimurium. Sickled cells may also be visually observed in poorly oxygenated blood of a patient with sickle cell anemia. Because of such complications, the prophylactic administration of penicillin has significantly reduced morbidity and mortality from pneumonia in children <3 years of age57, but prophylaxis is recommended to be continued through age 5. Vaccines that are recommended for patients with homozygous sickle cell include all standard pediatric vaccines as well as pneumococcal 23-valent polysaccharide vaccine at 2 and 5 years of age with a booster every 10 years. The pain typically lasts 2 to 6 days and should be managed with narcotic analgesics (morphine or morphine derivatives). Narcotic addiction may occur over time but can be prevented by providing the patient with only a few days supply of analgesics following the crisis. Stroke most commonly occurs in the first decade of life, whereas intracerebral hemorrhage is a complication associated with adulthood. As a result, patients might experience reduced potassium excretion, hyperuricemia, hematuria, hyposthenuria, and renal failure. Men experiencing occlusion of the corpus cavernosum can experience acute or chronic priapism. Investigators have observed that patients with HbF levels >20% experience a relatively mild or benign course with fewer vaso-occlusive crises. The use of hydroxyurea in the sickle cell population should be carefully weighed for risk-versus-benefit, because this drug is a cytotoxic agent associated with bone marrow suppression. Patients taking hydroxyurea should have bone marrow studies performed before therapy and periodically during therapy. Following initiation of hydroxyurea therapy, blood counts should be monitored closely and the dose adjusted accordingly. Several clinical trials evaluating hydroxyurea show improvement in the clinical course of patients with sickle cell anemia. During early childhood, he experienced several episodes of acute pain, swelling of the hands and feet, and jaundice. Recently, frequent blood transfusions have reduced the frequency of sickling crises. He has a pulse of 110 beats/minute, a respiratory rate of 18 breaths/minute, and a temperature of 98. His lungs are clear, and cardiac auscultation reveals a hyperdynamic pericardium and a systolic murmur at the left sternal edge. Splenomegaly rapidly evolves over several hours and is accompanied by progressive anemia. The low reticulocyte count is consistent with acute sequestration because a reticulocyte response would be expected if the anemia had developed in recent days. The hyperdynamic pericardium and systolic murmur are consistent with the high cardiac output required to deliver oxygen in an anemic state. Because patients with sickle cell anemia often lose the ability to concentrate urine, they may become dehydrated, which further contributes to cell sickling. Splenectomy may be indicated in instances of severe splenomegaly, repeated infarction, or pain in adults, and it is indicated when crises occur in children. Those patients with sickle cell anemia who are bedridden should be placed on chronic heparin therapy to prevent vascular occlusions and deep vein thrombosis. Unless a concurrent deficiency of vitamin B12, folate, or iron exists, administration of vitamin supplements is not of value. Although serum iron often is decreased, reticuloendothelial iron stores are usually adequate, and treatment with iron is not warranted. Serum iron and total ironbinding capacity are most often decreased, whereas iron stores (as reflected by serum ferritin) are usually normal or increased.
These medicine 3x a day buy thorazine 50 mg fast delivery, like keratin medicine 3605 order thorazine 100 mg with visa, smoothed the skin surface and also reduced hyperpigmentation of the skin symptoms celiac disease thorazine 100 mg free shipping. As a result medications 2355 generic thorazine 100mg on-line, soybean extract targets cellular enzymes to prevent keratinocyte apoptosis symptoms genital warts purchase thorazine 100 mg fast delivery, decreases transepidermal water loss and the level of inflammation to protect from skin damage due to photoaging symptoms 22 weeks pregnant cheap thorazine 50mg otc. This occurs by inhibition of enzymes that mediate keratinocyte phagocytosis of melanosomes. The gel and cream were not irritating, and showed no sign of erythema or edema on the skin of shaved rabbits. The use of these rice-based cosmeceuticals on 30 volunteers resulted in a thicker epidermis in a majority of them, and skin lightening, more elasticity, and improvement of roughness in a minority of the study group. This prevents liquid accumulation under the eyes and decreases eye puffiness, as well as improving skin elasticity. Two studies showed that acetyl tetrapeptide-5 reduced under-eye puffiness and discoloration. Silk fibrin is known for its immune tolerance, and is notable for its historic use in suturing. At first, silk sericin was considered an impurity that elicited harmful pro-inflammatory cytokine production. Tyrosinases catalyze the hydroxylation of monophenol molecules in cells, turning them into ortho-quinones. Antioxidant effects and inhibitory effects on tyrosinase were also recently discovered to be found in the Anti-Aging Topical Peptides and Proteins 153 non-protein layer of silkworms, which consists of carbohydrates, salt, wax, and flavonoid derivatives. A hydroxyproline assay showed no significant differences in hydroxyproline content, skin impedance, and transepidermal water loss between sericin treated skin and control. A silk sericin-releasing bioactive wound dressing was developed and found on average to heal faster, in 12 days, compared to Bactigras dressing, which healed in 14 days with significantly reduced pain. By inhibiting the activity of innervating neurons, downregulation of muscle activity could lead to a decrease in wrinkles. Although Btx has shown efficacy in clearing facial wrinkles, it has a high toxicity and has to be used with strict medical protocols, limiting its topical or at-home use. Topical use of 10% argireline resulted in a reduced depth and roughness of periorbital wrinkles in 10 healthy women. This peptide, an elongated version of argireline, showed a similar efficacy in reducing wrinkles. In one study that used 10% acetyl octapeptide-3 topically, after 28 days periorbital wrinkles were significantly reduced by nearly 35%. One active controlled trial compared 5% leuphasyl solution to 5% argireline and a combination of 5% leuphasyl and 5% argireline. This study showed comparable effects of these two drugs on wrinkles when used singly, and when used together, they resulted in a synergistic and more powerful reduction of wrinkles. Pentapeptide-3, or Vialox, is a synthetic peptide that acts on a different part of the neuromuscular junction. As a competitive antagonist at nicotinic acetylcholine receptors, Vialox prevents the sodium influx required for muscle fibers to depolarize and contract. Within one minute of treatment, muscle contracts can be reduced by up to 71%, and 58% of muscle fibers are still immotile two hours later. In one study, Vialox used twice a day for 28 days resulted in a nearly 50% reduction in wrinkle depth and roughness. This neurotoxin also binds reversibly to nicotinic acetylcholine receptors at the neuromuscular junction, preventing depolarization and contraction of the muscle. Tripeptide-3 is an oligopeptide that mimics the role of Wagerlin-1 on the neuromuscular junction at a 0. In vivo studies demonstrated nearly a 50% decrease in wrinkle size after 28 days of treatment with 4% Tripeptide-3 applied to the face twice daily. Many of these peptides are as efficacious as tretinonin, with much less skin irritation. However, a substantial amount of topical peptides presented in this chapter require more research in permeation ability, especially in aged skin, and need to be better characterized with randomized double-blind controlled trials to measure their abilities to decrease wrinkles, increase skin elasticity, and treat other effects of aging on their target populations. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: Structure, function, and biochemistry. Ultraviolet radiation and skin aging: Roles of reactive oxygen species, inflammation and protease activation, and strategies for prevention of inflammation-induced matrix degradation. Transdermal delivery of molecules is limited by full epidermis, not just stratum corneum. Transdermal protein delivery by a coadministered peptide identified via phage display. Size and stability optimization for polyurethane nanostructures used as transdermal drug vehicle. Nanodesign of olein vesicles for the topical delivery of the antioxidant resveratrol. Intracellular delivery of major histocompatibility complex class I-binding epitopes: Dendritic cells loaded and matured with cationic peptide/poly(I:C) complexes efficiently activate T cells. Evaluation of histologic and electron microscopic changes after novel treatment using combined microdermabrasion and ultrasound-induced phonophoresis of human skin. Screening of chemical penetration enhancers for transdermal drug delivery using electrical resistance of skin. The weak rate of sphingolipid biosyntheisis shown by keratinocytes isolated from aged vs. Synthetic tripeptide which increases survival of normal liver cells, and stimulates growth of hepatoma cells. Experimental influence of pharmacological agents on the regeneration of nervous tissue in vitro. Influence of selected peptides and their copper complexes on antioxidant enzyme activities in human skin fibroblasts. Expression of glycosaminoglycans and small proteoglycans in wounds: Modulation by the tripeptide-copper complex glycyl-L-histidyl-Llysine-Cu(2+). Expression and localization of the two small proteoglycans biglycan and decorin in developing human skeletal and non-skeletal tissues. In vivo stimulation of connective tissue accumulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine in rat experimental wounds. Effects of copper tripeptide on the growth and expression of growth factors by oral and irradiated fibroblasts. Human skin retention and penetration of a copper tripeptide in vitro as function of skin layer towards anti-inflammatory therapy. Effects of topical copper tripeptide complex on wound healing in an irradiated rat model. Biological activities of selected peptides: Skin penetration ability of copper complexes with peptide. Effects of topical creams cntaining vitamin C, a copper-binding peptide cream and melatonin compared with tretinoin on the ultrastructure of normal skin. A clinical evaluation of a copper-peptide-containing liquid foundation and cream concealer designed for improving skin condition [press release]. Transdermal delivery of proteins mediated by non-covalently associated arginine-rich intracellular delivery of peptides. Teaching the basics of redox biology to medical and graduate students: Oxidants, antioxidants and disease mechanisms. Regulation of extracellular matrix production by chemically synthesized subfragments of type I collagen carboxy propeptide. Efficacy of anti-aging products for periorbital wrinkles as measured by 3-D imaging. A novel L-ascorbic acid and peptide conjugate with increased stability and collagen biosynthesis. Activation of latent transforming growth factor beta 1 and inhibition of matrix metalloprotease activity by a thrombospondin-like tripeptide linked to elaidic acid. Modulation of cellular senescence in fibroblasts and dermal papillae cells in vitro. Elevation of the antifibrotic peptide N-acetyl-seryl-aspartyl-lysylproline: A blood pressure-independent beneficial effect of angiotensin I-converting enzyme inhibitors. Kinetin-induced differentiation of normal human keratinocytes undergoing aging in vitro. Depigmentation and rejuvenation effects of kinetin on the aged skin of hairless descendants of Mexican hairless dogs. Prevage blend of cosmetic functional ingredients counteracts skin aging by providing anti-oxidant and anti-inflammatory protection. A clinical study of topical Pyratine 6 for improving the appearance of photodamaged skin. Bone morphogenetic protein signalling regulates keratinocyte proliferation and migration during wound healing in murine and human skin. Topical application of epidermal growth factor accelerates wound healing by myofibroblast proliferation and collagen synthesis in rat. The receptor for advanced glycation end products is highly expressed in the skin and upregulated by advanced glycation end products and tumor necrosis factoralpha. A natural extracellular factor that induces Hsp72, inhibits apoptosis, and restores stress resistance in aged human cells. Use of a keratin-based hydrogel in the management of recessive dystrophic epidermolysis bullosa. An anti-aging effect on the lips and skin observed in in vivo studies on a new fibronectin-like peptide. Anti-photoaging effects of soy isoflavone extract (aglycone and acetylglucoside form) from soybean cake. A comparison of biological activities of a new soya biopeptide studied in an in vitro skin equivalent model and human volunteers. Novel aspects of intrinsic and extrinsic aging of human skin: Beneficial effects of soy extract. Differential effects of exogenous and endogenous hyaluronan on contraction and strength of collagen gels. Anti-aging efficacy of topical formulations containing niosomes entrapped with rice bran bioactive compounds. Properties and antityrosinase activity of sericin from various extraction methods. Isolation and bioactivities of a non-sericin component from cocoon shell silk sericin of the silkworm Bombyx mori. Fibroin and sericin from Bombyx mori silk stimulate cell migration through upregulation and phosphorylation of c-jun. Clinical potential of a silk sericin-releasing bioactive wound dressing for the treatment of split-thickness skin graft donor sites. The anti-wrinkle efficacy of argireline, a synthetic hexapeptide, in Chinese subjects: A randomized, placebo-controlled study. Biological activities of selected peptides: Skin penetration ability of copper complexes with peptides. Effect of various penetration enhancers: In vitro study across hairless mouse skin. A clinical evaluation of a copper-peptide-containing liquid foundation and cream concealer designed for improving skin condition. Effects of topical creams containing vitamin C, a copper-binding peptide cream and melatonin compared with tretinoin on the ultrastructure of normal skin. Topical palmitoyl pentapeptide provides improvement in photoaged human facial skin. Use of a facial moisturizer containing palmitoyl pentapeptide improves the appreance of aging skin. Kinetin containing lotion compared with retinol containing lotion; Comparable improvements in the signs of photoaging. Improvement in the appearance of wrinkles with topical transforming growth factor beta(1) and l-ascorbic acid. Human growth factor and cytokine skin cream for facial skin rejuvenation as assessed by 3D in vivo optical skin imaging. Cosmetic effectiveness of topically applied hydrolysed keratin peptides and lipids derived from wool. Blanes-Mira C, Clemente J, Jodas G, Gil A, Fernandez-Ballester G, Ponsati B et al. There are 20 kinds of naturally occurring amino acids with optical active structures at -position (L-amino acids) except glycine. Greenstein and Winitz said: "Few products of natural origin are versatile in their behavior and properties as are the amino acids, and few have such a variety of biological duties to perform" in their preface of Chemistry of the Amino Acid in 1961. This is due to the market growth and cost reduction of certain amino acids for many industrial applications. For example, in food applications there is huge and still growing consumption generated for glutamic acid (Glu) and glycine (Gly) as food additives and aspartic acid (Asp) and phenylalanine (Phe) as raw materials for the artificial sweetener "aspartame. Cysteine (CysH) and proline (Pro) are major amino acids utilized in the flavor industry to manufacture natural flavors by Maillard reaction with sugars. Health food and pharmaceutical intermediates are other rapidly growing markets for many amino acids. In this chapter, the role of amino acids and derivatives are reviewed as functional molecules for cosmeceutical applications. Amino Acids Basic Features As stated in Chemistry of Amino Acids:1 Amino acids are at once water soluble and amphoteric electrolytes, with the ability to form acid salts and basic salts and thus act as buffers over at least two range of pH; dipolar ions of high electric moment with a considerable capacity to increase the dielectric constant of the medium in which they are dissolved; compounds with reactive groups capable of a wide range of chemical alterations leading readily to a great variety of degradation, synthetic, and transformation products such as esters, amides, amines, polymers, etc.
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