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Artificial recharge grameen herbals lukol 60 caps, which is becoming an increasingly important resource management option herbals and anesthesia cheap lukol master card, can also introduce water of different origin and quality into aquifers herbals for kidney function purchase lukol 60 caps free shipping. This of course means that groundwater recharge is not always of the same good quality as infiltrating rainfall herbals shops buy lukol 60caps on line, which itself may be contaminated by acid rain or atmospheric acid deposition. Infiltration of rainfall on high ground occurs in a recharge area in which the hydraulic head decreases with depth, and net saturated flow is downwards away from the water table and laterally towards areas of lower hydraulic head (A in Figure 2. After moving slowly through the aquifer down the hydraulic gradient (B in Figure 2. In a recharge area, the water table can be at depth, with a considerable thickness of unsaturated zone above it. In a discharge area, the water table is usually at, or very near to, the ground surface. Rivers, canals, lakes and reservoirs may either discharge to or receive recharge from groundwater, and the relationship may change seasonally or over a longer time span or along the course of a single river. While in many cases groundwater and surface water catchments have more or less the same boundaries, this is not always the case. Seasonally due to recharge, and in response to heavy abstraction, groundwater catchment boundaries may deviate significantly from surface water catchments. In deep aquifers, or sequences of more than one layered aquifer, groundwater recharge may come from great distances and deep groundwater flow may have little relationship to the overlying surface water system. In most cases, however, if there is no information it is a reasonable first estimate to assume surface water and groundwater catchments are similar and that groundwater flow patterns are likely to be a subdued reflection of the surface topography. Groundwater occurrence and hydrogeological environments 37 In large, deep aquifers, groundwater is likely to move slowly, at rates of a few metres per year, from recharge to discharge area over tens or hundreds of kilometres. This may take hundreds or thousands of years, and typical order-of-magnitude values from time of recharge to point of discharge are indicated in Figure 2. Hydrogeologists can confirm these by isotopic dating techniques (Kendal and McDonnel, 1998; Edmunds and Smedley, 2000). In small, shallow aquifers, recharge and discharge areas may be much closer or even adjacent to each other, and residence times can be restricted to a few months or years. In arid and semi-arid regions, groundwater discharge areas are often characterized by poor quality groundwater, particularly with high salinity. Groundwater discharge may be from seepages or salt marshes with distinctive vegetation, known as salinas or playas, in which evapotranspiration at high rates for long periods of time has led to a build-up in salinity. In unconsolidated aquifers, both hydraulic conductivity and porosity usually decrease with depth due to consolidation and compaction. In fractured aquifers too, the hydraulic conductivity and porosity provided by the fracture system would be expected to decline with depth as the fractures become less open. This general but variable and not easily predicted decline in groundwater flow properties with depth often restricts the flow and pollutant pathway to the most permeable, near-surface parts of the aquifer. Further, the zone of seasonal water table fluctuation is often where the most active solution of fractures occurs and this helps to enhance the flow dominance of the uppermost part of the saturated aquifer. Even in humid areas, recharge comprises only a proportion of the total rainfall and a simple calculation will show that, for typical annual recharge volumes equivalent to tens to a few hundreds of millimetres, the total volume of groundwater in storage in the aquifer is many times larger than the annual recharge. Aquifers are generally, therefore, high storage, low recharge systems with substantial capacity for dilution of incoming pollutants, except in the situations of restricted shallow flow referred to immediately above. In these cases, incoming recharge may be distributed far from evenly through the aquifer, and the resulting groundwater volume available for dilution may be much less than the total storage of the aquifer. However, geodiversity and the consequent hydrogeological variability are poorly appreciated by many of those working in water protection and management. The variability both between and within hydrogeological environments can have a profound impact on how aquifers respond to the pressures imposed upon them. Further, if an aquifer is to be protected and managed, it is important to understand the groundwater flow system to be able to assess the susceptibility of the aquifer to these external changes and the types and timescales of the likely responses. While almost all geological materials contain some water and many different rocks can form useful aquifers, nevertheless it is possible to develop a summary of the most common aquifer types and hydrogeological environments (Table 2. This classification is a useful overall basis for helping to identify the major potential concerns for protection and management of groundwater. While such a broad classification is useful, it inevitably involves some simplifications of the true breadth of subsurface geological variation and complexity. At one end of the scale are extensive sequences of coastal, river and deltaic alluvium, sometimes hundreds of metres thick. These unconsolidated sedimentary deposits form some of the most important aquifers in the world, in which very large Groundwater occurrence and hydrogeological environments 39 volumes of groundwater are stored and from which large quantities of water are pumped for water supply and irrigation. Examples include the Lower Indus and Ganges Brahmaputra valleys, the Mekong, the Tigris-Euphrates, the north European plain and the Nile valley. As an example, aquifers within the unconsolidated sediments underlying the Huang-Hai-Hai 2 Plain of eastern China, which covers an area of 350 000 km, provide the potable water requirements for nearly 160 million people and also enough to irrigate some 20 million ha of land. Groundwater in these sediments can be subdivided into three types: an upper unconfined freshwater zone, a middle saline water zone and a lower confined aquifer. The total 3 volume of groundwater stored exceeds 2 000 000 million m, whilst usable groundwater 3 resources have been estimated at more than 49 000 million m /a. Other unconsolidated sedimentary aquifers may be much less extensive but can still store sufficient volumes of groundwater to be important sources of water supply. Smaller but still locally-important aquifers are provided by river valley and coastal plain sediments of more limited lateral extent and depth, and aquifers of much more restricted size and extent may occur in upland river valleys as river terraces. Aquifers in unconsolidated strata are rarely simple homogeneous systems but typically consist of alternating permeable layers of productive sands and gravels separated by less permeable aquitard layers of clay and silt, reflecting the complex history of deposition. In such sequences, the shallowest aquifer may be the easiest and cheapest to exploit, but is likely to be the most vulnerable to pollution. The presence of aquitards may produce complex groundwater flow patterns, but the permeable horizons may still have a degree of hydraulic continuity, such that pumping from one layer will affect the others, producing significant vertical head gradients and consequent leakage. Intermontane alluvial and volcanic systems Aquifers of this type include some volcanic lavas and pyroclastic rocks, together with alluvial-volcanic and alluvial fan deposits. They are typically associated with rapidly infilled and faulted troughs or basins within mountain regions (Table 2. When combined with the above average rainfall that is often found in the mountainous climatic regimes where many of these environments are found, valuable aquifers occur and are capable of supporting substantial borehole yields. Additional recharge to groundwater often occurs 40 Protecting Groundwater for Health where surface water flowing from the surrounding mountain slopes infiltrates into the highly permeable valley-fill deposits, especially through the alluvial fans and colluvial deposits found on valley margins. Examples of this environment include Mexico City, Guatemala City, San Salvador, Managua and San Jose in Central America, the Kathmandu Valley in Nepal, Bandung and Yogyakarta in Indonesia, Davao in the Philippines and Sana?a in Yemen. In these mountainous areas, flat land is limited and highly valuable, and is often densely populated. Restrictions on available land for settlement will often result in groundwater abstraction for potable supplies in the basin occurring within densely populated areas, with significant implications for water quality. Furthermore, the concentration of population and the consequent high water demand can result in groundwater abstraction exceeding the safe yield of the aquifer. Consolidated sedimentary aquifers Important aquifers occur within consolidated sedimentary strata, principally sandstone and limestone (Table 2. These can be broadly subdivided into younger, Tertiary formations and older Mesozoic or Palaeozoic formations. Globally, although their distribution is irregular, they are widespread and common being found both in mountain belts such as the Alpine-Himalayan, Andean, Urals and North American cordilleras and in lowlands and plateau areas such as northern Europe and central China. Sandstones have been formed when sandy marine or continental sediments were buried and compacted to form consolidated rocks. Thus the younger, Tertiary sandstones usually retain some degree of primary porosity between the sand grains and are typically of low to moderate permeability. In the older, Mesozoic or Palaeozoic formations with more strongly developed cementing of the grains, the primary porosity may have become largely eliminated. Pre-Tertiary sandstones can range from friable to highly indurated depending on the degree of cementation, and in the latter cases it is the secondary porosity resulting from the development of fractures which can provide adequate permeability and storage for such rocks to form productive aquifers. Limestones exhibiting solution enhancement of such fractures (called karst) are widespread and can be prolific aquifers, although well yields are highly variable in time and space. For instance, in northern China, karst limestones occupy an area of 2 800 000 km, are typically 300-600 m thick and their groundwater resources have been 3 -1 estimated at 12 800 million m yr.

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Unfortunately, there have been in approximately 50% of untreated seropositive persons. Counseling of the provider should treatment, prophylactic regimens can prevent opportunis? include "safer sex" guidelines. Prophylaxis and early intervention prevent several infectious diseases, including 7. Recommendations for screening tests, vaccinations, screen blood and blood products have lowered the risk of and prophylaxis are listed in Table 31-4. Thus, in this Hepatitis B vaccine for those who are hepatitis B surface antigen population, a nonreactive treponema! In addition, persistence of trepo? 6 months; repeat if no immunity 1 month after three-vaccine nemes inthe spinal fuid afer one dose ofbenzathine peni? series. Those with can switch to longer intervals (see Complications, Section M) a normal cerebrospinal fuid evaluation are treated as hav? Consider anal swabs for cytologic evaluation ing late latent syphilis (benzathine penicillin G, 2. However, it is not known if it is efficacious in preventing herpes zoster in this population. There is also the possibility of transmis? ment-prophylactic regimens can safely be discontinued. Substance abuse treatment susceptible to a number of opportunistic pathogens, the should be recommended for persons who are using recre? use of agents with activity against more than one pathogen ational drugs. To reduce the likelihood candidiasis should be offered primary prophylaxis for of infection with Bartonella species, patients should avoid Pneumocystis pneumonia. Patients with a history ofPneu? activities that might result in cat scratches or bites. Medication Dose Side Effects Limitations Trimethoprim? One double-strength tablet Rash, neutropenia, hepatitis, Hypersensitivity reaction is common but, if mild, sulfamethoxazole three times a week to one Stevens-Johnson it may be possible to treat through. Atovaquone 1500 mg orally daily with a Rash, diarrhea, nausea Less efective than suspension trimethoprim? meal sulfamethoxazole; equal eficacy to dapsone, but more expensive. Aerosolized 300 mg monthly Bronchospasm (pretreat with Apical P jirovecii pneumonia, extrapulmonary pentamidine bronchodilators); rare P jirovecii infections, pneumothorax. Clarithromycin (500 mg orally twice daily) and episodes ofPneumocystis pneumonia develop while taking azithromycin (1200 mg orally weekly) have both been prophylaxis tend to have milder courses. Prophylaxis against M avium complex infection the use of epoetin alfa has also decreased. Trimethoprim-sulfamethoxazole (one double-strength tablet daily) offers good protection against toxoplasmosis, as does a combination of pyrimethamine, 25 mg orally C. Antiretroviral Therapy once a week, plus dapsone, 50 mg orally daily, plus leucovo? the availability of agents that in combination suppress rin, 25 mg orally once a week. Cessation of secondary prophylaxis because medication resistance to antiretroviral agents for Pneumocystis pneumonia is described above. For example, patients with second or third episodes achieves undetectable viral load has been shown to provide of Pneumocystis pneumonia may have developed allergic a durable response to the therapy. For? maintain virologic control over time, combination ther? tunately, there are several alternatives available for the apy with at least three medications from at least two treatment of Pneumocystis infection. Common Side Medication Dose Effects Special Monitoring1 Cost2 Cost/Month Didanosine (ddl) 400 mg orally daily (enteric Peripheral neuropa Bimonthly neurologic S12. When administered with efavi? renz, fosamprenavir/ritonavir, tipranavir/ritonavir, or rifampin: 50 mg twice daily. When administered to inte? grase-experienced patients with suspected integrase resistance: 50 mg twice daily. Source: Red Book (electronicversion),Truven Health Analytics Info rmation. Zid? For hospitalized patients, initiating treatment in patients ovudine and didanosine are the most likely to cause neutro? with opportunistic infections requires close coordination penia. Stavudine is the most likely to cause lipoatrophy (loss between inpatient and outpatient clinicians to ensure that of fat in the face, extremities, and buttocks) followed by treatment is continued once patients are discharged. Didanosine, lamivudine, Although theideal combination of medications hasnotyet emtricitabine, and tenofovir can be administered daily. Most commonly used nucleoside/nucleotide reverse transcriptase inhibitor backbone. Although it contains three medications it Zidovudine 300 mg does notconstitute a complete treatment. Source: Red Book (electronic version), Truven Health Analytics Information. Side effects seen with zidovudine reaction developing is high; the reaction is characterized are listed in Table 31-6. Approximately 40% ofpatients expe? by a fu-like syndrome with rash and fever that worsens rience subjective side effects that usually remit within 6 with successive doses. The common dose-limiting side effects are anemia allele does not guarantee that the patient will avoid the and neutropenia, which require ongoing laboratory moni? hypersensitivity reaction. The dosage is 150 mg orally twice daily or an increased risk of myocardial infarction in some cohort 300 mg orally once a day. There are no significant side effects who have underlying risks of cardiovascular disease. However, lamivu? fixed-dose combination pill with lamivudine for use as a dine can be dosed daily, eliminating the special indication once daily pill (Epzicom; Table 31-7). As is true of lamivudine, emtricitabine Abacavir is also formulated with zidovudine and lami? has activity against hepatitis B and its dosage should be vudine in a single pill (Trizivir, one tablet orallytwice daily; reduced in patients with chronic kidney disease. In particular, the K103N this reason, it appears to cause less harm to kidneys, less mutation does not appear to have an impact on etravirine bone resorption, and appears to have stronger antiviral (or rilpivirine). The major side effects are rash and psychiat? didanosine (ddi) is the enteric-coated capsule. For adults ric/neurologic complaints, with patients reporting symp? weighing at least 60 kg, the dose is one 400-mg enteric? toms ranging from lack of concentration and strange coated capsule orally daily; for those 30-59 kg, the dose is dreams to delusions and mania. Didanosine wane over time, usually within a month or so; however, should be taken on an empty stomach. Participant incidence of pancreatitis with didanosine is 5-10%-of level data from four randomized trials of efavirenz regi? fatal pancreatitis, less than 0. Patients with a history of mens versus non-efavirenz containing regimens found pancreatitis, as well as those taking other medications asso? increased suicidality (hazard ratio of2. Administration of efavirenz with food, espe? methoxazole and intravenous pentamidine) are at higher cially fatty food, may increase its serum levels and risk for this complication. Because of the side-effect pro? not be used in patients with baseline viral loads of 100,000 fle, didanosine is rarely used today. As is true rophy, lipodystrophy, peripheral neuropathy and, rarely, of efavirenz, rilpivirine is available in a once-daily fixed? lactic acidosis and hepatitis, stavudine (d4T) should no dose combination with tenofovir and emtricitabine (Com? longer be used except when there is no alternative. Amprenavir has been rapine should be used only when there is not a better almost entirely replaced by its prodrug, fosamprenavir. Unfortunately, all Pis, with the exception of unboosted atazanavir have been linked to a constellation of metabolic D. Etra? of the likelihood that increased levels of cholesterol and virine dosage is one 200-mg tablet twice daily. Patients cholesterol, and triglyceride levels performed every with signs of severe rash or hyersensitivity reactions 12 months. Clinicians should assess for coronary heart should immediately discontinue the medication. Fish oil (3000 mg daily) combined with exercise and dietary counseling has been found to 3. Protease inhibitors-Ten Pis-indinavir, nelfinavir, decrease triglyceride levels by 25%. Patients with persis? ritonavir, saquinavir, amprenavir, fosamprenavir, lopinavir tently elevated fasting serum triglyceride levels of 500 mg/ (in combination with ritonavir), atazanavir, darunavir, and dL or more who do not respond to dietary intervention tipranavir are available. Indinavir crystals are present in the urine in are known to induce the P450 system should be avoided.

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Putative confounding variables such as smoking bajaj herbals pvt ltd ahmedabad order lukol toronto, consumption of alcohol and coca leaves were included in the evaluation bestlife herbals buy lukol overnight. It was shown that the frequencies of micronuclei per 1000 binucleated cells in peripheral lymphocytes were significantly elevated in the arsenic-exposed groups as compared with controls (women herbals man alive discount lukol, 41 versus 8 zigma herbals lukol 60caps generic. In contrast, the frequencies of sister chromatid exchange in the arsenic-exposed group were not affected (5. Induction of sister chromatid exchange was found in peripheral lymphocytes of subjects after 20 years of exposure to arsenic in well-water (> 130 g/L) in Argentina (Lerda, 1994). Putative exposures to other genotoxic compounds were reported to be taken into account in the study. In a further evaluation, to homogenize the age of the exposed group, participants older than 50 years were excluded from the analysis. In the younger subset, no correlation between sister chromatid exchange and sex, or sister chro matid exchange and age was found. Sister chromatid exchange was induced by concen trations as low as 100 g/L arsenic for the younger subset. Moreover, the arsenic content in drinking-water was associated with the frequency of sister chromatid exchange in both sexes but was not affected by sex. Moreover, arsenic in urine was quantified by an insensitive colorimetric method of analysis. Arsenic (sodium arsenite) did not induce tryptophan revertants in Escherichia coli or ouabain or 6-thioguanine-resistant mutants in Chinese hamster lung (V79), Chinese hamster ovary or Syrian hamster embryo cells (Lee et al. However, sodium arse nite and sodium arsenate were mutagenic in mouse lymphoma L5178Y cells, inducing tri fluorothymidine-resistant mutants. Sodium arsenite induced a significantly increased frequency of sister chromatid exchange in Chinese hamster ovary and Syrian hamster embryo cells. Sodium arsenate was one order of magnitude less potent in inducing sister chromatid exchange than sodium arsenite. It induced the formation of micronuclei in Chinese hamster ovary and V79 cells in the cytokinesis-block micronucleus test using cytochalasin B as well as in the absence of cytochalasin B in V79 cells and also induced chromosomal aberrations in mammalian cells. Sodium arsenite significantly elevated the frequency of sister chromatid exchange and significantly enhanced micronucleus formation in isolated human peripheral lymphocytes as well as in whole blood after cytokinesis block through cytochalasin B. It induced chromosomal aberrations as chromatid gaps, fragmentation, endoreduplication and chromosomal breaks in human leukocytes, lymphocytes and primary umbilical cord fibro blasts. Moreover, induction of aneuploidy was observed in human peripheral lymphocytes treated with sodium arsenite in vitro, suggesting that this clastogenic agent may exhibit some weak aneuploidogenic properties. There is some evidence that human, mouse and rat leukocytes are more sensitive to the induction of micronuclei after treatment with arsenite than guinea-pig leukocytes (Peng et al. This difference in the induction of micronuclei by arsenic could not be explained by a species-dependent variability in arsenite methylation. The leukocytes of all four species were able to ethylate arsenic but there was no clear correlation between the ability to methylate arsenic and the induction of micronuclei. Arsenic sulfide (called orpiment) did not induce micronuclei to any quantifiable extent, presumably because of its low solubility and bioavailability, a reflection of elevated blood levels of arsenic in orpiment-treated animals. After oral or subcutaneous administration of sodium arsenite for either 1, 6 or 30 consecutive days, elevated frequencies of chromosomal aberrations were found in the bone-marrow cells of Swiss albino mice. Arsenite treatment increased genomic hypomethylation in a dose-dependent manner and reduced the frequency of methylation at several cytosine sites within the promoter region of the Ha-ras gene (Okoji et al. However, pretreatment with sodium arsenite resulted in a reduction in the mutagenicity of methyl methanesulfonate. It should be noted, however, that the trivalent species are formed in vivo after exposure to penta valent arsenic. Methylated trivalent arsenic is more toxic, and genotoxic, than trivalent inorganic arsenic; in contrast, methylated pentavalent arsenic is less toxic, and genotoxic, than pentavalent inorganic arsenic. These may play a role in the genomic instability that can result from treatment with arsenic. Arsenic appears to have little if any ability to induce point mutations (National Research Council, 1999, 2001). It impaired the incision step at low concentrations and the ligation step at higher concen trations (Hartwig et al. Inoculation of the latter cells into nude mice gave rise to malignant tumours (fibrosarcoma and metastases to the lung) (Lee et al. Stimulation of cell proliferation had been shown in normal human epidermal kera tinocytes treated in vitro by arsenic (Germolec et al. A reduction in p53 protein levels concomitant with an increase in mdm2 protein levels were also observed in a keratinocyte (HaCaT) cell line treated with arsenic. More recently, it has been discovered that a number of other regions have drinking-water that is highly contaminated with arsenic. In most of these regions, the drinking-water source is groundwater, naturally contaminated from arsenic-rich geological formations. In some areas of Japan, Mexico, Thailand and other countries, mining, smelting and other industrial activities have contributed to elevated concentrations of arsenic in local water sources. Levels of arsenic in affected areas may range from tens to hundreds or even thousands of micrograms per litre, whereas in unaffected areas levels are typically only a few micrograms per litre. Trace amounts of methylated arsenic species are typically found in drinking-water, and higher levels are found in biological systems. Inorganic arsenic (arsenate plus arsenite) is the predominant form of arsenic in drinking-water. In many areas where contamination of drinking-water by arsenic has been reported, current exposures have been reduced by various interventions. Informative epidemiological studies of cancer in relation to arsenic in drinking-water include ecological studies and fewer case?control and cohort studies. For most other known human carcinogens, the major source of causal evidence derives from case?control and cohort studies, with little evidence from ecological studies. In contrast, for arsenic in drinking-water, ecological studies provide important information for causal inference. As a conse quence of widespread exposure to local or regional water sources, ecological measurements provide a strong indication of individual exposure. Moreover, in the case of arsenic, the eco logical estimates of relative risk are often so high that potential confounding with known causal factors cannot explain the results. There is extensive evidence of increased risks for urinary bladder cancer associated with arsenic in drinking-water. All studies that involved populations with high long-term exposures found substantial increases in the risk for bladder cancer. In Taiwan, the evidence is supported by case?control studies and cohort studies within the exposed communities that demonstrate evidence of dose?response relationships with levels of arsenic in drinking-water. The evi dence of increased mortality from bladder cancer in Chile comes from a large population with exposure to arsenic in all major cities and towns of the contaminated region. There is also evidence of increased risks for bladder cancer from a small cohort study in Japan of persons drinking from wells that had been highly contaminated with arsenic wastes from a factory and an ecological study from Argentina with moderate exposure to arsenic in well-water. Two case?control studies that investigate low exposure to arsenic found increased risks with increasing exposure in one or more subgroups. Considered overall, the findings cannot be attributed to chance or confounding, and they are consistent, with strong associations found in populations with high exposure. Evidence for a dose?response relationship between arsenic in drinking-water and risk for lung cancer was also observed in ecological studies in Taiwan and Argentina, in cohort studies in south-western and north-eastern Taiwan and Japan and in case?control studies in south-western Taiwan and Chile. The potential confounding effect of cigarette smoking was ruled out by direct and indirect evidence in studies from Taiwan and Chile. Considered overall, the findings cannot be attributed to chance or confounding, are consistent and demonstrate strong associations in populations with high exposure. The recognition that arsenic was potentially carcinogenic arose from occurrences of skin cancer after ingestion of medicinal arsenic, arsenical pesticide residues and arsenic contaminated drinking-water. Skin cancer is a commonly observed malignancy related to contamination of drinking-water with arsenic. The characteristic arsenic-associated skin tumours include keratinocytic malignancies (non-melanoma skin cancers), in particular squamous-cell carcinomas, including Bowen disease, and multiple basal-cell carcinomas. Ecological studies, largely from the south-west of Taiwan, indicate substantially ele vated incidence of, prevalence of and mortality rates for skin cancer associated with drinking-water highly contaminated with arsenic, with evidence of a dose?response relationship. Findings in ecological studies were substantiated in two cohort studies in the region of Taiwan that is endemic for arsenic. A high prevalence of skin lesions, including skin cancers, was found in rural regions of Mexico. A cohort study from the south-west of Taiwan reported that differences in the levels of serum?

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Improved regimens capitalizing on the various benefcial effects of hydroxyacids should be explored herbals summit lukol 60 caps with visa. Development of a w/o/w emulsion for chemical peeling applications containing glycolic acid biotique herbals buy cheap lukol. Comparison and correlation between stinging responses to lotus herbals 3 in 1 lukol 60caps line lactic acid and bioengineering parameters herbals used for mood order lukol canada. Effects of various concentrations of glycolic acid at the corneoxenometry and collaxenometry bioassays. Clinical tolerance and effcacy of capryloyl salicylic acid peel compared to a glycolic acid peel in subjects with fne lines/wrinkles and hyperpigmented skin. Functional changes in human stratum corneum induced by topical glycolic acid: Comparison with all-trans retinoic acid. Modulation of stratum corneum properties by salicylic acid and all-trans-retinoic acid. Glycolic acid peels versus salicylic-mandelic acid peels in active acne vul garis and post-acne scarring and hyperpigmentation: A comparative study. Effcacy and safety of a new salicylic acid derivative as a complement of vitamin A acid in acne treatment. Increased in vivo collagen synthesis and in vitro cell collagen synthesis and in vitro cell proliferative effect of glycolic acid. Topical 8% glycolic acid and 8% L-lactic acid creams for the treat ment of photodamaged skin. Histometric assessment of the age-related skin response to 2-hydroxy-5-octanoyl benzoic acid. Center for Food Safety and Applied Nutrition Offce of Cosmetics and Colors Fact Sheet. Levy Introduction Retinoids and hydroxy acids have successfully been used as active ingredients to improve the appear ance of aging skin. However, both retinoids and hydroxy acids may be associated with skin irrita tion, stimulating a search for alternatives. Possible alternatives include kinetin (N6-furfuryladenine), zeatin, and pyratine-6. Kinetin and zeatin are members of a plant growth hormone family known as cytokinins, which have growth-promoting and antiaging effects in plants. Pyratine-6 (furfurylamino tetrahydropyranyladenine) is a synthetic analog of kinetin. It is a naturally present base modifcation3 and is present in both plants4,5 and human cell extracts. Zeatin contains adenine with the addition of an hydroxy-methylbutyl group (Figure 9. Cytokinins are plant growth substances that promote cell division and possibly cell differentiation. Plant-based studies are responsible for most of the data regarding the biological properties of kinetin. Low levels of kinetin stimulate calcium infux through plant cell plasma membranes. Both relatively young and old cells were studied: fbro blasts that had completed less than 20% and older cells that had completed 90% or more of their potential in vitro life span were studied (Table 9. The studied cellular manifestations of in vitro aging included cell enlargement, presence of multi-nucleated giant cells, accumulation of cellular debris and lipofuscin, and changes in actin flaments and microtubules. Kinetin did not alter the overall proliferation or the longevity of the cultured cells. Similar results were reported with zeatin with less toxicity at higher concentrations. A diet containing 20?50 ppm kinetin fed to fruit fies prolonged average and maximum life span by 65% and 35%, respectively. Kinetin has inhibitory activity on free radical formation of active platelets in vitro and thrombus for mation in vivo. A cytokinin nucleoside, N6-fufuryladenosine, has been shown to have antiproliferative and apopto genic activity against various human cancer cell lines,17 although similar activity has not been shown with kinetin. Kinetin may function as a natural antoxidant,21 preventing the formation of reactive oxygen species, or as a direct free radical scavenger. However, pluripotency may serve as a required prerequisite to act effectively as an agent of antiaging. There was no signifcant difference in trans dermal absorption with the two test formulations. Topical treatment with low concentrations of kinetin lead to a more homogenous dispersion of melanin granules in the epidermis of dogs as well as reduced the stratum corneum thickness. The overall photodamage was reported 94 Cosmeceuticals and Active Cosmetics improved by both self-assessment and dermatologist grading. Transepidermal water loss was decreased after 24 weeks, which is consistent with an improvement in the stratum corneum barrier function. Ninety-eight subjects with mild to moderate photodamaged facial skin applied a kinetin-containing lotion and creams for 10 weeks (Revlon Research Center, unpublished studies). All subjects were assessed at baseline 4, 8, and 10 weeks for photodamage parameters. Statistically signifcant improvements were noted in all parameters, greatest with texture, skin clarity, discrete and mottled pigmentation, fne wrin kling, and global appearance. Forty female subjects who ranged in age from 22 to 57, having mild to moderate facial skin photo damage, participated in a 12-week, split face, double-blind, controlled, and randomized study compar ing a topical retinol against a topical kinetin-containing lotion twice daily (Almay Research?poster exhibit American Academy of Dermatology meeting, New Orleans, Louisiana, February 2002). Evaluations at four-week intervals demonstrated signifcant improvements for all attributes graded including discrete and mottled pigmentation, fne wrinkling, and overall photodamage. The kinetin containing lotion was found to have greater improvements in texture and clarity. Controlled use testing for up to six weeks demonstrated no signifcant irritation (Almay research, unpublished studies). Subjects were treated with once daily application of 2 mg/cm2 at six sites on the mid back over two weeks. No difference in the minimal erythema dose was demonstrated between untreated control and treated sites. These fndings suggest that kinetin has minimal potential to cause irritation, allergy, or photosensitization. A 12-week open label study on photoaging utilized furfuryl tetrahydropyranyladenine (Pyratine-6). Improvements in hyperpigmentation, skin roughness, wrinkling, and moisturization were noted. Conclusion Kinetin (N6-furfuryladenine), a plant growth regulator, delays a range of cellular changes associated with the aging of human skin cells in vitro. Isolation, structure, and synthesis of kinetin, a substance promot ing cell division. Cytokinin controls the cell cycle at mitosis by stimulating the tyrosine dephophorylation and activation of p34cdc-2-like H1 histone kinase. Cytokinin stimulates dihydropyridine-sensitive calcium uptake in moss pro toplasts. Genomodulatory and youth-preserving effects of zeatin on human skin fbro blasts undergoing aging in vitro. Plant growth hormone kinetin delays ageing, prolongs the lifespan and slows down development of the fruitfy Zaprionus parvittiger. Increased longevity of kinetin-fed Zaprionus fruitfies is accompanied by their reduced fecundity and enhanced catalase activity. Inhibitory acticity of kinetin on free radical formation of active platelets in vitro and on thrombus formation in vivo. Kinetin-induced premature aging and altered differentiation of normal human epidermal keratinocytes undergoing aging in vitro. Hormetic modulation of differentiation of normal human epidermal keratinocytes undergoing replicative senescence in vitro. Relative assessment of oxidative stress protection capacity compared to commonly known antioxidants. Depigmentation and rejuvenation effects of kinetin on the aged skin of hairless descendents of Mexican hairless dogs. Effcacy of cosmetic formulations containing disper sion of liposome with magnesium ascorbyl phosphate, alpha-lipoic acid and kinetin.