Anisha Chandiramani, MD

• Medical Instructor in the Department of Medicine

https://medicine.duke.edu/faculty/anisha-chandiramani-md

This diabetes signs and symptoms pictures order 2mg repaglinide with amex, in turn diabetes test before eating repaglinide 1 mg otc, triggers vigorous proliferation and vascularization of the tumor tissue and suppresses their further differentiation diabetes insipidus dogs treatment generic repaglinide 1 mg. This explains why in grapevine cuttings inoculated wounds below developing and auxin-producing leaf buds produce vigorously growing tumors in contrast to wounds opposite the buds diabetes mellitus lada discount 2 mg repaglinide amex. Accordingly diabetes medications newest discount 0.5 mg repaglinide mastercard, naturally occurring crown galls develop on grapevine only in spring diabetes in dogs blindness purchase repaglinide 0.5 mg with visa, when the dormancy callose plugs in the phloem are degraded during the incipient basipetal auxin flow (Aloni and Peterson, 1991; Aloni et al. The strongest fluorescence was detected within the concentric tumor bundles in the parenchyma cells of developing phloem and xylem. Within the pathological xylem, predominantly parenchyma cells were labeled, in contrast to the multiseriate rays. The amount of free zeatin (tZ) clearly peaked at 4 weeks pi with an eightfold increase (Figure 15-3c). The large cytokinin nucleotide pool steadily increased during tumor development and attained 16times that of the controls. Tumorized plants develop only poor roots with particularly few lateral roots (Figure 15-2f and Mistrik et al. The structural peculiarities such as vessels of decreasing diameter and the multiplication of rays that remain unlignified suggested that ethylene plays a crucial role in tumor development (Aloni et al. Indeed, ethylene emission by the tumors was shown to be up to 140 times that by control stems of tomato and Ricinus (Aloni et al. Good aeration is supported by the peripheral aerenchyma of the tumor and in the former cortex tissue. It is characterized by cell enlargement, lysis and large intercellular spaces (Wдchter et al. In contrast to water-logged plants, tumors emit more ethylene in re-watered plants after mild water deficiency (Wдchter et al. Correspondingly, downward bending of cotyledons and leaves are typical for tumorized plants (Aloni et al. Distinct fluorescence was detected around the vascular bundles and in the very peripheral cell layers. As early as 1 week pi its accumulation is maximum but then rapidly decreases, after 4 weeks even below the concentration in the control stem (Figure 15-3g). The initial rapid increase is not due to a mere wound effect, since concentrations in both unwounded healthy and wounded but non-inoculated tissue were the same. Only such high auxin and cytokinin concentrations enable the continuous differentiation of functional phloem and xylem in the tumors, while they simultaneously suppress root and shoot differentiation out of the tumor parenchyma. Subsequently, ethylene induces the accumulation of abscisic acid, not only in the tumor periphery for activating osmoprotectants but also in the host leaves where it re-directs the nutrient bearing water and sieve tube flow via the auxin and ethylenedependent enlarged xylem and phloem into the tumor by inducing host leaf stomata closure. Revising old assumptions of lacking connections of the host bundle with the tumor vessels, the transport of negatively-charged dyes, amido black, acid fuchsin and the fluorescent pyrenetrisulfonate clearly visualized a continuous and efficient water flow through the vessels from the host stem into the tumor, up to its surface (Schurr et al. However, tumor water loss contributes little change to the water flow to host shoots. The water vapour conductance (gH2O) of tumors rises rapidly within the first week after infection, with the strongest increase between the 2nd and 3rd week pi (Wдchter et al. The highly irregular tumor surface area increases almost linearly with tumor growth. During the dark period, gH2O of the leaves decreases to a value which is only half of that of the tumors, i. However, the transpiration rate of leaves of tumor-infected plants is typically only 10% of that of non-infected plants (Veselov et al. The remaining transpiration in leaves of tumorized plants is still 150 times that of the tumor in light. But this phytohormone signaling from the tumor to the host shoot has to be regarded as the crucial step in the water regime of the host plant with substantial consequences for nutrient partitioning between the host shoot and the tumor. The leaves closest to the tumor have a spectacular 10-fold lower gH2O than leaves of non-tumorized plants, but it clearly increases with increasing distance from the tumor. Similarly, leaves at the shoot apex of non-tumorized plants, when supplied with 0. In accordance there is no nitrate reducing activity detectable in tumors in contrast to the control stem or leaves (0, 0. To know how the inorganic nutrients efficiently accumulate in the tumor sink tissue, plasma membrane electropotentials (Em) were determined (Pavlovkin et al. Xylem and phloem parenchyma cells and stem/tumor-located rays hyperpolarized to about -170 mV (controls were 120 to -140 mV), indicating high plasma membrane proton pump activities, as suggested earlier by Ramaiah and Mookerjee (Ramaiah and Mookerjee, 1982). The patterns of individual cell electropotentials in excised tissue sections were supplemented by whole organ voltage measurements. These trans-tumor electropotentials confirm the findings of respiration-dependent and phytohormonestimulated high plasma membrane proton pump activity in intact tumors, mainly in the xylem and phloem parenchyma cells (Pavlovkin et al. The existence of back-to-back electrogenic H+ pump activity across the boundary membrane of the organ surface and across the xylem parenchyma symplast/xylem interface has been demonstrated (Okamoto et al. In Kalanchoл leaf tumors, concentration of sucrose was 14times, fructose 40times, glucose 25times, and total amino acids up to 10times higher than in the control leaf tissue. In Ricinus stem tumors, sucrose was maximally increased to 20times and amino acids up to 40times the control values (Mistrik et al. Since solute concentrations change with time and in local distribution (periphery vs. Since the photosynthetic activity of leaf crown galls is only about 25% of that of control leaves (Marx and Ullrich-Eberius, 1988), organic nutrients have to be imported via the phloem. Not only the phloem, but also the ray parenchyma cells are functional in lateral transmission of both solutes and virus across the stem. These results were recently confirmed for the mechanism of phloem unloading in the syncytium of nematode-induced root giant cells (Hoth et al. Hence, not only the tumor xylem is well coupled with the host vessels, but also the sieve elements are tightly, functionally and effectively connected to the phloem of the host and are symplastically unloaded into the tumor parenchyma tissue. Concurrent activities and sites of action for enzymes of sucrose metabolism changes are the following: Vacuolar invertase predominates during initial import of sucrose into the symplastic continuum, corresponding to hexose concentrations in expanding tumors. Later, sucrose synthase and cell wall invertase activities rise in the tumor periphery to modulate both sucrose accumulation and decreasing turgor for import by metabolization. Sites of abscisic acid immunolocalization correlate with both central vacuolar invertase and peripheral cell wall invertase. Roles in vascular bundles are indicated by sucrose synthase immunolocalization in xylem parenchyma for inorganic nutrient uptake and in the phloem, where the resolution allowed sucrose synthase identification in sieve elements and companion cells. The time course of acid cell wall invertase activity is clearly independent of initial phloem unloading, which confirms the existence of symplastic phloem unloading, excluding a major function of acid cell wall invertase in primary phloem unloading of sucrose. The osmoprotectant proline accumulates almost simultaneously with the activity of the acid cell wall invertase (Wдchter et al. Ann Bot Aloni R (1979) Role of auxin and gibberellin in differentiation of primary phloem fibres. Plant Physiol 63: 609-614 Aloni R (2004) the induction of vascular tissue by auxin. Kluwer, Dordrecht, pp 471-492 Aloni R, Peterson C (1991) Seasonal changes in callose levels and fluorescein translocation in the phloem of Vitis vinifera L. Planta 196: 597-605 Aloni R, Raviv A, Peterson C (1991) the role of auxin in the renewal of dormancy callose and resumption in the phloem activity in Vitis vinifera L. Ulmer Verlag, Stuttgart Bopp M, Leppla E (1964) Ein Vergleich der Histogenese der Wurzelhalsgallen an Blдttern und Sprossachsen von Kalanchoe daigremontiana. Plant Cell Environ 8: 587-594 Deeken R, Engelmann J, Efetova M, Mьller T, Kaiser W, Palme K, Schartl M, Dandekar T, Hedrich R (2005) An integrated view of gene expression and solute profiles in Arabidopsis tumour cells: a genome-wide approach. Plant J 34: 778-787 Dehio C (2004) Molecular and cellular basis of Bartonella pathogenesis. Annu Rev Microbiol 58: 365-390 Dehio C (2005) Bartonella-host-cell interactions and vascular tumour formation. Nat Rev Microbiol 3: 621-631 Feussner I, Wasternack C (2002) the lipoxygenase pathway. Bot Acta 111: 130-136 Folkman J (1971) Tumor angiogenesis: therapeutic implications. Phytochemistry 65: 169-179 Gaymard F, Pilot G, Lacombe B, Bouchez D, Bruneau D, Boucherez J, MichauxFerriиre N, Thibaud J-B, Sentenac H (1998) Identification and distribution of Biology of Crown Gall Tumors 587 a Shaker-like outward channel involved in K+ release into the xylem sap. Plant Physiol 121: 291-299 Hansen H, Grossmann K (2000) Auxin-induced ethylene triggers abscisic acid biosynthesis and growth inhibition. Plant Physiol 124: 1437-1448 Heller W, Forkmann G (1993) Biosynthesis of flavonoids. Academic Press, New York, pp 373-390 Hoth A, Schneidereit A, Lauterbach C, Scholz-Starke J, Sauer N (2005) Nematode infection triggers the de novo formation of unloading phloem that allows macromolecular trafficking of green fluorescent protein into syncytia. Plant Physiol 27: 335-354 Kupila-Ahvenniemi S, Therman E (1968) Morphogenesis of crown gall. Plant Sci 57: 27-36 Mathesius U (2001) Flavonoids induced in cells undergoing nodule organogenesis in white clover are regulators of auxin breakdown by peroxidase. Plant Physiol 107: 323-329 Okamoto H, Ichino K, Katou K (1978) Radial electrogenic activity in the stem of Vigna unguiculata: involvement of spatially separate pumps. Am J Clin Oncol 26: 92-94 Schell J, Koncz C, Spena A, Palme K, Walden R (1994) the role of phytohormones in plant growth and development. Plant Physiol 95: 480-485 Stenlid G (1976) Effects of flavonoids on the polar transport of auxins. Arnold Constable, London Weil M, Rausch T (1990) Cell wall invertase in tobacco crown gall cells: enzyme properties and regulation by auxin. Planta 153: 326-337 Winter-Sluiter E, Lдuchli A, Kramer D (1977) Cytochemical localization of K+stimulated adenosine triphosphatase activity in xylem parenchyma cells of barley roots. The Ti plasmids of Agrobacterium tumefaciens carry almost all of the genes required for the formation of crown gall tumors and for the utilization of opines that are produced by these tumors. These plasmids also encode a cell-cell signalling (quorum sensing) system that is homologous to the LuxR-LuxI system of Vibrio fischeri. The traR gene is induced by particular opines, causing quorum sensing in this bacterium to occur only in the presence of these compounds. TraR activates genes required for conjugal transfer and vegetative replication of the Ti plasmid. Populations of bacterial cells appear to use a variety of types of chemical signalling to coordinate diverse activities, especially those activities requiring large numbers of bacterial cells. For example, many types of pathogenic bacteria communicate during colonization of plant or animal hosts, and thereby coordinate their attack. It is thought that single cells are more susceptible to host defences than a population of bacteria that coordinately express genes involved in virulence. For example, species of Erwinia that cause soft rot on plants do not produce lytic enzymes in their plant hosts until a threshold population density is reached (Perombelon, 2002; Smadja et al. In biofilm formation, communication between neighbouring cells must occur for the complex structures that are associated with biofilms to form (Parsek and Greenberg, 2005). Swarming motility is another example of behaviour where cell-cell communication is a critical component (Eberl et al. The importance of cell-cell communication in bacteria is also reflected by the fact that these systems have evolved numerous times. Many gram positive bacteria use short peptides as intercellular signalling molecules (Dunny and Leonard, 1997; Lyon and Novick, 2004). When it accumulates to some threshold level, it binds to the LuxR protein, which then forms dimers and activates transcription of target genes that direct bioluminescence (Choi and Greenberg, 1991, 1992a, 1992b; Stevens et al. Vibrio fischeri colonizes the light organs of certain species of squid and fish to high population the Cell-Cell Communication System of Agrobacterium Tumefaciens 595 densities. The term quorum sensing is often used for these systems to reflect the importance of population density for the accumulation of the signal molecules, which must reach some threshold level before a coordinated response occurs (Fuqua et al. However, it should also be pointed out that a diffusion barrier must also be present for the system to work, so that the signal can accumulate in the growing population (Redfield, 2002). LuxR-LuxI type systems have been described in a number of plant pathogens, including Pseudomonas syringae, P. Similar systems have also been identified on the symbiosis plasmids in the related nitrogen-fixing plant symbionts, such as Rhizobium sp. Most studies of this system have focussed on the molecular biology of TraI, TraR, and the other proteins involved in regulating the activity of TraR. Our knowledge of the importance and activity of the TraR-TraI system in pathogenesis and establishment of A. In this review, we will focus on the current state of our knowledge of this system from a molecular perspective. In the last section, we will speculate on the adaptive significance of this system. When this signal accumulates to a threshold level (in the nanomolar range), it binds to its intracellular target the LuxR-type protein TraR (Piper et al. It should be noted that four additional luxR homologs are present in the genome sequence of C58 (Goodner et al. A model of the TraR-TraI system in octopine-type Ti plasmids is presented in Figure 16-1, and discussed in the following sections. A composite gene map and sequence is available for the octopine-type plasmids R10, A6, B6, Ach5, and 15966, and for the nopaline-type pTiC58 from the genome sequence of strain C58 (Zhu et al. On both types of plasmids, expression of the traR gene is positively regulated by the presence of specific opines: octopine for octopine-type and agrocinopines A and B for nopaline-type Ti plasmids (Genetello et al. On octopine-type Ti plasmids, traR is the last gene of the occ operon, which is divergently transcribed from occR (Fuqua and Winans, 1996b). In the presence of octopine, OccR activates expression of the occ operon, which directs octopine uptake and utilization (Figure 16-1). On nopaline-type Ti plasmids, traR is the fourth gene in the five gene arc operon, which is not related to the occ operon described above (Beck von Bodman et al. The arc operon, required for agrocinopine A and B utilization, is divergently transcribed from the acc operon, the first gene of which is accR. In the presence of agrocinopine A or B, repression of both the arc and acc promoters by AccR is relieved, resulting in gene expression (Beck von Bodman et al. For chrysopine-type Ti plasmids, the conjugal opines are agrocinopines C and D, and traR is thought to be negatively regulated by AccR (Oger and Farrand, 2001).

Diseases

• Achard syndrome
• Purpura, thrombotic thrombocytopenic
• Rickettsialpox
• Systemic arterio-veinous fistula
• Brachydactyly type A6
• Parkinsonism

The median ammonia concentration in freeway stormwater is almost three times the median concentration observed in residential and open-space land uses diabetes treatment vitamins buy repaglinide 0.5 mg without a prescription, while freeways have the lowest orthophosphate and nitrite­nitrate concentrations-half of the concentration levels that were observed in industrial land uses blood glucose 80 mg dl discount repaglinide 1 mg with visa. In almost all cases the median metal concentrations at the industrial areas were about three times the median concentrations observed in open-space and residential areas managing diabetes shift work discount repaglinide 2mg on line. The highest lead and zinc concentrations (but not necessarily the highest median concentrations) were found in industrial land uses diabete 96 repaglinide 1mg with mastercard. By contrast diabetes keywords repaglinide 0.5mg on-line, the highest concentrations of dissolved and total phosphorus were associated with residential land uses blood glucose kits for dogs cheap repaglinide 1 mg otc. Fecal coliform concentrations are also relatively high for residential and mixed residential land uses. Open-space land-use areas show consistently low concentrations for the constituents examined. There was no significant difference noted for total nitrogen among any of the land uses monitored. The median values are indicated with the horizontal line in the center of the box, while the ends of the box represent the 25th and 75th percentile values. The whickers extend to the 5th and 95th percentile values, and values outside of these extremes are indicated with separate dots. These groups were statistically analyzed and were found to have at least one group that is significantly different from the other groups. The ranges of the values in each group are large, but a very large number of data points is available for each group. The grouping of the data into these categories helps explain much of the total variability observed, and the large number of samples in each category allows suitable statistical tests to be made. In contrast, fecal coliforms and total dissolved solids were found to be higher in the upper Midwest. More detailed discussions of land use and regional differences in stormwater quality can be found in Maestre et al. In addition to the information presented above, numerous researchers have conducted source area monitoring to characterize sheet flows originating from urban surfaces (such as roofs, parking lots, streets, landscaped areas, storage areas, and loading docks). This discussion provides some additional information concerning industrial stormwater beyond that included in the previous discussion of municipal stormwater. In general, there is a profound lack of data on industrial stormwater compared to municipal stormwater, and a correspondingly greater uncertainty about industrial stormwater characteristics. The first comprehensive monitoring of an industrial area that included stormwater, dry weather base flows, and snowmelt runoff was conducted in selected Humber River catchments in Ontario (Pitt and McLean, 1986). Table 3-5 shows the annual mass discharges from the monitored industrial area in North York, along with ratios of these annual discharges compared to discharges from a mixed commercial and residential area in Etobicoke. Stormwater runoff from "hotspots" may contain loadings of hydrocarbons, trace metals, nutrients, pathogens and/or other toxicants that are greater than the loadings of "normal" runoff. Examples of these hotspots include airport de-icing facilities, auto recyclers/junkyards, commercial garden nurseries, parking lots, vehicle fueling and maintenance stations, bus or truck (fleet) storage areas, industrial rooftops, marinas, outdoor transfer facilities, public works storage areas, and vehicle and equipment washing/steam cleaning facilities (Bannerman et al. The elevated concentrations and mass discharges found in stormwater at industrial sites are associated with both the activities that occur and the materials used in industrial areas, as discussed in the sections that follow. Effects of Roofing Materials on Stormwater Quality the extensive rooftops of industrial areas can be a significant pollutant source area. A summary of the literature on roof-top runoff quality, including both roof surfaces and underlying materials used as subbases (such as treated wood), is presented in Table 3-6. During pilot-scale tests of roof panels exposed to rains over a two-year period, Clark et al. These results indicated that copper continued to be released from these wood products at levels high enough to exceed aquatic life criteria for long periods after installation, and were not simply due to excess surface coating washing off in the first few storms after installation. Traditional unpainted or uncoated hot-dip galvanized steel roof surfaces can also produce very high zinc concentrations. The authors concluded that traditional galvanized metal roofing contributed the greatest concentrations of many metals and nutrients. In addition, they found that pressure-treated and waterproofed wood contributed substantial copper loads. Other researchers have investigated the effects of industrial rooftop runoff on receiving waters and biota. For example, concrete is often mixed with industrial waste sludges as a way of disposing of the wastes. However, this can lead to stormwater discharges high in toxic compounds, either due to the additives themselves or due to the mobilization of compounds via the additives. Salaita and Tate (1998) showed that high levels of aluminum, iron, calcium, magnesium, silicon, and sodium were seen in the cement-waste samples. A variety of sands, including waste sands, have been suggested as potential additives to cement and for use as fill in roadway construction. In addition to the bitumens and asphalts, other compounds are added to paving (and asphaltic roofing) materials. Chemical modifiers are used both to increase the temperature range at which asphalts can be used and to prevent stripping of the asphalt from the binder. Reclaimed asphalt pavements have also been proposed for use as fill materials for roadways. Brantley and Townsend (1999) performed a series of leaching tests and analyzed the leachate for a variety of organics and heavy metals. Only lead from asphalt pavements reclaimed from older roadways was found to be elevated in the leachate. Fish kills have been reported when rains occur shortly after asphalt has been installed in parking areas near ponds or streams (Anonymous, 2000; Perez-Rivas, 2000; Kline, 2002). It is expected that these effects are associated with losses of the more volatile and toxic hydrocarbons that are present on new surfaces. It is likely that the concentrations of these materials in runoff decrease as the pavement ages. Toxicity tests conducted on pavements several years old have not indicated any significant detrimental effects, except for those associated with activities conducted on the surface (such as maintenance and storage of heavy equipment; Pitt et al. However, pavement maintenance used to "renew" the asphalt surfaces has been shown to cause significant problems, which are summarized below. Consequently, the City of Austin has restricted the use of parking lot coal-tar sealants, as have several Wisconsin communities. Stored Materials Exposed to Rain Although roofing and pavement materials make up a large fraction of the total surface covers and can have significant effects on stormwater quality, leaching of rain through stored materials may also be a significant pollutant source at industrial sites. Exposed metals in scrap yards can result in very high concentrations of heavy metals. For example, Table 3-7 summarizes data from three metals recycling facilities/scrap yards in Wisconsin and shows the large fraction of metals that are either dissolved in the runoff or associated with very fine particulate matter. For most of these metals, their greatest abundance is associated with the small particles (<20 µm in diameter), and relatively little is associated with the filterable fraction. These metals concentrations (especially zinc, copper, and lead) are also very high compared to that of most outfall industrial stormwater. Dry weather flows, snowmelt, and atmospheric deposition all contribute to the pollutant loading of urban areas to receiving waters, and for some compounds may be the largest contributor. Dry Weather Flows At many stormwater outfalls, discharges occur during dry weather. These may be associated with discharges from leaking sanitary sewer and drinking water distribution systems, industrial wastewaters, irrigation return flows, or natural spring water entering the system. Possibly 25 percent of all separate stormwater outfalls have water flowing in them during dry weather, and as much as 10 percent are grossly contaminated with raw sewage, industrial wastewaters, and so forth (Pitt et al. These flow contributions can be significant on an annual mass basis, even though the flow rates are relatively small, because they have long duration. This is particularly true in arid areas, where dry weather discharges can occur daily. Furthermore, in the nearby Ballona Creek watershed, dry weather discharges of trace metals were found to comprise from 8 to 42 percent of the total annual loading (McPherson et al. Stein and Tiefenthaler (2003) further found that the highest loadings of metals and bacteria in this watershed discharging during dry weather can be attributed to a few specific stormwater drains. The following photographs show various nontraditional sources of contaminants in urban runoff. Snowmelt In northern areas, snowmelt runoff can be a significant contributor to the annual discharges from urban areas through the storm drainage system. In locations having long and harsh winters, with little snowmelt until the spring, pollutants can accumulate and be trapped in the snowpack all winter until the major thaw when the contaminants are transported in shortduration events to the outfalls (Jokela, 1990). The sources of the contaminants accumulating in snowpack depend on the location, but they usually include emissions from nearby motor vehicles and heating equipment and industrial activity in the neighborhood. Dry deposition of sulfur dioxide from industrial and power plant smokestacks affects snow packs over a wider area and has frequently been studied because of its role in the acid deposition process (Cadle, 1991). The sources of directly deposited pollutants include debris from deteriorated roadways, vehicles depositing petroleum products and metals, and roadway maintenance crews applying salt and anti-skid grit (Oberts, 1994). Urban snowmelt, like rain runoff, washes some material off streets, roofs, parking and industrial storage lots, and drainage gutters. However, snowmelt runoff usually has much less energy than striking rain and heavy flowing stormwater. However, erosion of bare ground at construction sites in the spring due to snowmelt can still be very high. Construction site in early spring after snowmelt showing extensive sediment transport. Sources of Contaminants in Snowmelt Several mechanisms can bring about contamination of snow and snowmelt waters. Initially, air pollutants can be incorporated into snowflakes as they form and fall to the ground. After it falls to the ground and accumulates, the snow can become further contaminated by dry atmospheric deposition, deposition of nearby lost fugitive dust materials (usually blown onto snow packs near roads by passing vehicles), and wash off of particulates from the exposed ground surfaces as it melts and flows to the drainage system. Snowflakes can remove particulates and gases from the air by in-cloud or below-cloud capture. In-cloud capture of pollutants can occur during snowflake formation as super-cooled cloud water condenses on particles and aerosols that act as cloud condensation nuclei. This is known as nucleation scavenging and is a major pathway for air pollution to be incorporated into snow. Snowflakes are more effective below-cloud scavengers than raindrops because they are bigger and fall slower. Most of the contamination of snow in urban areas likely occurs after it lands on the ground. Table 3-8 shows the flow-weighted mean concentrations of pollutants found in undisturbed falling snow compared to snow found in urban snow cover (Bennett et al. Pitt and McLean (1986) also measured snowpack contamination as a function of distance from a heavily traveled road passing through a park. The contaminants in the snow were at much greater concentrations near the road (the major source of blown contamination on the snow) than farther away. They concluded that "pollutant levels at the dump site are the result of environmental input occurring after the snow falls. Similar roadside snowpack observations along city park roads by Pitt and McLean (1986) also indicated the strong association of road salt with snowpack chloride levels. Runoff and Pollutant Loading from Snowmelt Snowmelt events can exhibit a first flush, in which there are higher concentrations of contaminants at the beginning compared to the total event averaged concentration. The enrichment of the first portion of a snowmelt event by soluble pollutants may be due to snowpack density changes, where water percolation and melt/freeze events that occur in the snowpack cause soluble pollutants to be flushed from throughout the snowpack to concentrate at the bottom of the pack (Colbeck, 1981). This concentrated layer leaves the snowpack as a highly concentrated pulse, as snow melts from the bottom due to warmth from the ground (Oberts, 1994). Also, the large volume of melt plus rain can wash off pollutants that have accumulated on various surfaces such as roads, parking lots, roofs, and saturated soil surfaces. The intensity of runoff from a rain-on-snow event can be greater than a summer thunderstorm because the ground is saturated or frozen and the rapidly melting snowpack provides added runoff volume (Oberts, 1994). Figure 3-28 compares the runoff volumes associated with snowmelts alone to those associated with snowmelts mixed with rain from monitoring at an industrial area in Toronto (Pitt and McLean, 1986). Rain with snowmelt contributes over 80 percent of the total cold-weather event runoff volume. Whether pollutant loadings are higher or lower for snowmelt than for rainfall depends on the particular pollutant and its seasonal prevalence in the environment. For example, the high concentrations of dissolved solids found in snowmelt are usually caused by high chloride concentrations that stem from the amount of de-icing salt used. Figure 3-29 is a plot of the chloride concentrations in the influent to the Monroe Street detention pond in Madison, Wisconsin. Chloride levels are negligible in the non-winter months but increase dramatically when road salting begins in the fall, and remain high through the snow melting period, even extending another month or so after the snowpack in the area has melted. Nutrients were much lower for snowmelt, while the loadings for lead were about the same for both forms of precipitation. Oberts (1994) reports that much of the annual pollutant yields from event flows in Minneapolis is accounted for by end-of-winter major melts. End-of winter melts yielded 8 to 20 percent of the total phosphorous and total lead annual load in Minnesota. Box 3-8 shows mass pollutant discharges for a study site in Toronto and emphasizes the significance of snowmelt discharges on the total annual storm drainage discharges. Atmospheric Deposition the atmosphere contains a diverse array of contaminants, including metals. These contaminants are introduced to the atmosphere by a variety of sources, including local point sources. These emissions, composed of gases, small particles (aerosols), and larger particles, become entrained in the atmosphere and subject to a complex series of physical and chemical reactions (Schueler, 1983).

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Maintenance doses Increase progressively until clinical effect or unwanted effects (particularly vomiting) supervene diabetes rash buy repaglinide 2mg online. Tablets may be crushed and dispersed in water immediately prior to administration blood sugar imbalance symptoms discount repaglinide 2mg online. Also available: Sinemet 110 (carbidopa 10:levodopa 100 mg); Sinemet Plus (carbidopa 25:levodopa 100 mg); and Sinemet 275 (carbidopa 25 mg:levodopa 250 mg) diabetic diet sugar grams buy repaglinide 1mg fast delivery. Important interactions and unwanted effects Sudden onset of sleep metabolic disease in animals order 0.5mg repaglinide with visa, excessive sedation blood glucose gestational diabetes 2mg repaglinide fast delivery. Mannitol Neurological indications Emergency treatment of known or suspected cerebral oedema syndrome x type 2 diabetes discount 2mg repaglinide. Important interactions and unwanted effects Hypovolaemia due to obligatory diuresis. Comments A transient artefactual hypertonic hyponatraemia typically occurs on initial use (the mannitol causes water shift from the intracellular to the extracellular compartment and a dilutional hyponatraemia with normal total body Na). Preparations Standard capsule (1, 2, 3, 5 mg) and 2 mg controlledrelease tablet (3 mg). Treatment with a combination of standard and controlled-release preparation has been described. Use in visual impairment argued on the basis of loss of physiological light/dark sleep cues. Methylphenidate Neurological indications Treatment of attention-deficit hyperactivity disorder. Consider initial and subsequent blinded trials omitting doses: ideally with a semi-objective symptom severity measure. Many children with attention-deficit hyperactive disorder may have a co-existing epilepsy. Typically given morning and midday, or controlled-release preparation once daily in the morning. Important interactions and unwanted effects Rapid infusion may be associated with severe hypertension and cardiovascular collapse. Dosing Buccal use as rescue treatment Buccal administration Neonate: 300 microgram/kg as a single dose. Rapid intravenous injection 150­200 microgram/kg followed by continuous infusion of 1 microgram/kg/min (increase by 1 microgram/ kg/min every 15 min until seizure control). Sedation for procedures By intravenous injection over 2­3 min, 5­10 min before procedure. Pharmacokinetic data suggest the rate of metabolism and clearance in children is higher than in young adults. Important interactions and unwanted effects Rapid intravenous injection (<2 min) may cause seizure-like myoclonus in preterm neonates. Monitor closely, watch for respiratory depression, laryngospasm, bronchospasm, respiratory arrest, hypotension, heart rate changes, cardiac arrest, anaphylaxis. Rarely involuntary movement on withdrawal, paradoxical excitement and aggression, urinary retention, and incontinence. Important interactions and unwanted effects Has strong muscarinic action, and concomitant atropine or propantheline treatment may be required to treat abdominal cramps, excess salivation or diarrhoea. Nitrazepam Neurological indications Treatment of myoclonic seizures in infants and third-line treatment of infantile spasms. Dosing Starting doses and escalation regimen 125 microgram/kg po at night increasing by 125 microgram/kg/24 h increments divided in 3 doses every 3­4 days. Discontinuation regimen 75% of the dose for 2 months; 50% of the dose for 2 months; 25% of the dose for 2 months: then stop. Dosing Starting doses and escalation regimen 25 mg po once daily increasing by 25 mg/24 h increments every 7 days. Discontinuation regimen 75% for 2 weeks; 50% for 2 weeks; 25% for 2 weeks; then stop. A past history of rash formation with carbamazepine is a relative, but not absolute contraindication to oxcarbazepine use, although extra caution is required. Can be directly substituted (without a transition period) for carbamazepine: typical starting dose of oxcarbazepine = 150% of the prior carbamazepine dose. Contraindications Situations where poor adherence likely; unsuitable family and social situations (controlled drug); alcohol-dependency; sleep apnoea. Important interactions and unwanted effects Nausea, salty taste, headache, enuresis, bowel habit alterations. If therapy has been stopped for more than 14 consecutive days it should be recommenced at the initial starting dose and re-titrated. Important interactions and unwanted effects Frequent rectal administration can result in proctitis. Do not leave undiluted in a plastic syringe for any longer than necessary as it will dissolve the syringe: dilute and administer promptly! Missed dose regimen If one or more doses have been missed and breakthrough seizures have occurred, consider giving a single additional partial loading dose. Preparations Tablets (15, 30, and 60 mg; may be crushed), elixir (unpleasant taste; some preparations contain alcohol), intravenous injection (60 mg/mL, 200 mg/mL). Comments Aim for trough levels of 15­40 mg/L, although higher levels may be acceptable if there are no signs of toxicity. Dose requirements are toward the top end of this range (sometimes higher) in neonates and infants. Missed dose regimen If one or more doses have been missed and breakthrough seizures have occurred, consider giving an additional partial loading dose. Preparations As phenytoin sodium: capsules (25, 50, 100, and 300 mg); tablets 100 mg; As phenytoin: chewable Infatabs (50 mg); suspension (various strengths) injection 50 mg/mL. Important interactions and unwanted effects Nausea, headache, tremor, ataxia (dose-dependent). Osteomalacia (consider calcium/vitamin D supplementation if prolonged treatment is anticipated). Gum hyperplasia may be limited by scrupulous attention to teethcleaning (it is accelerated by the presence of plaque). Dental surgeons can offer cosmetic gum resection in established cases where continuing phenytoin use is required. Phenytoin is highly protein bound and levels may need to be adjusted for serum albumin. Nasogastric feeds should be suspended for 1­2 h before and after oral/ enteral phenytoin to improve absorption. Intravenous phenytoin infusion is strongly alkaline and must be infused slowly into a large vein to avoid phlebitis and/or tissue injury due to extravasation. Due to its need for conversion to phenytoin it is not clear that the faster infusions of fosphenytoin possible necessarily lead to earlier establishment of therapeutic brain phenytoin levels. Intravenous infusions of both fosphenytoin and phenytoin have been associated with severe cardiac arrhythmias. It is common to see inexperienced prescribers struggling with over- and undershooting levels. The main reason for this is failure to appreciate how long it takes to establish a new steady-state drug level after a dose change, 2 which is often several days and for phenytoin can be up to 2 weeks. The loading dose does not influence the steady-state level ultimately achieved, which is determined solely by the maintenance dose. Thus, if a blood level is still low and seizures are occurring a few days after starting phenytoin, give a further partial load. Adjustments of maintenance doses in light of steady-state blood levels should be in small increments (<10% previous dose). Important interactions and unwanted effects Some sedation, serious arrhythmias; glycosuria and rarely hyponatraemia. Dosing Initially 150 mg/kg/24h in 2­3 divided doses to a maximum of 300 mg/ kg/24 h in 2­3 divided doses. Important interactions and unwanted effects Weight gain, nervousness, hyperkinesia, and less commonly drowsiness, and depression. Dosing Starting doses and escalation regimen 5­12 yrs: 500 microgram po at night initially. Important interactions and unwanted effects Dry mouth, constipation, increased appetite and weight gain, drowsiness. Prednisolone (prednisone) Neurological indications Treatment of infantile spasms and epileptic encephalopathies. Dosing Starting doses and escalation regimen Infantile spasms: 10 mg qds for 14 days; increasing to 20 mg tds after 7 days if no response. Maintenance doses Infantile spasms: if not controlled after 7 days increase to 20 mg tds for 7 days. Discontinuation regimen Infantile spasms: if taking 10 mg qds for 14 days, reduce by 10 mg every 5 days then stop. If dose increased to 20 mg tds for 7 days, reduce to 40 mg/24 h for 5 days then 20 mg/24 h for 5 days then 10 mg/24 h for 5 days then stop. Comments Prolonged steroid treatment over months requires monitoring of bone mineral density and calcium/vitamin D supplementation. Gastric protection with a protonpump inhibitor or H2-antagonist may be required at high doses or prolonged courses. Pregabalin Neurological indications Neuropathic pain and paraesthesiae; also adjunctive treatment of focal seizures). Dosing Starting doses and escalation regimen Over 12 yrs: 75 mg/24 h divided in 3 doses; 75 mg/24 h increments at weekly intervals. Procyclidine Neurological indications Emergency treatment of acute dystonia and oculogyric crises. Dosing Maintenance doses 2­12 yrs: up to 60 mg/24 h divided in 2­3 doses (max 4 mg/kg/24 h). Preparations Tablets (10, 40, 80, and 160 mg), oral solution (5 mg/5 mL, 10 mg/5 mL, 50 mg/5 mL). Important interactions and unwanted effects Postural hypotension at excessive doses. Dosing Starting doses and escalation regimen Neonate: 5­10 mg/dose (give 1 h before feeds) repeated as required up to 4­6-hourly. Important interactions and unwanted effects Nausea, vomiting, increased salivation, abdominal cramps. Pyridoxal phosphate Neurological indication Refractory epilepsy in infants (may be superior to pyridoxine). Pyridoxine (vitamin B6) Neurological indications Treatment of refractory epilepsy in infants (see b p. Preparation Tablets (10, 20, and 50 mg; can be halved, quartered, or crushed and dissolved in water), injection (50 mg/2 mL), liquid. Try not to make any other changes in anti-epileptics during this period to aid interpretation (see b p. The dose for optimal neurodevelopmental outcome may be greater than the dose that controls seizures. Dosing Starting doses and escalation regimen Movement disorder: over 12 yrs, 1 mg/24 h divided in 2 doses increasing at weekly intervals by 1 mg/24 h if required. Maintenance doses Movement disorder: over 12 yrs, up to 4 mg/24 h divided in 2 doses. Comments Use of antipsychotics to manage acutely disturbed behaviour should only be considered in extreme situations. Rufinamide Neurological indications Epilepsy, particularly Lennox-Gastaut syndrome. Dosing Child 4­18 years less than 30 kg: 100 mg bd increasing if required by 100 mg bd at 7­14-day intervals; max. Preparations 100, 200, and 400 mg tablets, which may be crushed and mixed with water. Important interactions and unwanted effects May raise phenytoin levels; metabolism inhibited by valproate. Comments A serious hypersensitivity syndrome has been reported in children after initiating therapy; consider withdrawal if rash or signs or symptoms of hypersensitivity syndrome develop. Stiripentol Neurological indications Anti-epileptic drug particularly for severe myoclonic epilepsy of infancy (Dravet Syndrome). Dosing Starting doses and escalation regimen Child 3­18 years: initially 10 mg/kg in 2­3 divided doses; titrate dose over minimum of 3 days to max. Comments Most commonly used in conjunction with valproate and/or clobazam in treatment of severe myoclonic epilepsy of infancy (see b p. Important interactions and unwanted effects Antimuscarinic effects; may cause agitation in low dose, hepatitis. Contraindications Vasospasm, previous cerebrovascular accident or transient ischaemic attack, peripheral vascular disease, hypertension. Important interactions and unwanted effects Taste disturbance, mild irritation or burning sensation in the nose or throat, heat, heaviness, pressure or tightness, flushing in any part of the body, dizziness, weakness, fatigue, drowsiness and transient increases in blood pressure. Other triptans are not direct equivalents: rizatriptan has a short half-life, and frovatriptan has a much longer half-life than sumatriptan. Important interactions and unwanted effects Interacts with metoclopramide: increased risk of dystonia. Dosing Starting doses and escalation regimen Over 12 yrs: 5 mg bd for 1 week po increased by 5­10 mg/24 h divided in 2 doses every 5­7 days. Maintenance doses 30­45 mg/24 h po divided in 2­3 doses as tolerated and according to response. Important interactions and unwanted effects Nausea, diarrhoea, sleepiness, tremor, rarely non-convulsive status epilepticus. Important interactions and unwanted effects Interacts with ciprofloxacin and phenytoin. Important interactions and unwanted effects Nausea, anorexia with weight loss, paraesthesiae. Dosing Starting doses and escalation regimen 3 months­18 yrs: 1­2 mg/24 h po in 1 or 2 divided doses incrementing by 1 mg/24 h every 3­7 days, divided in 3­4 doses according to response.

Beta-Phenyl-Gamma-Aminobutyric Acid (Phenibut). Repaglinide.

• What is Phenibut?
• How does Phenibut work?
• Anxiety; alcoholism; heart arrhythmia; fear; insomnia; tension; stress; fatigue; post-traumatic stress disorder (PTSD); depression; and improving memory, learning, and cognition.
• Are there safety concerns?
• Dosing considerations for Phenibut.

Source: http://www.rxlist.com/script/main/art.asp?articlekey=97127

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