Metal Complexes of Curcumin for Cellular Imaging, Targeting, and Photoinduced Anticancer Activity

CONSPECTUS: Curcumin is a polyphenolic species. As an active ingredient of turmeric, it is well-known for its traditional medicinal properties. The therapeutic values include antioxidant, anti-inflammatory, antiseptic, and anticancer activity with the last being primarily due to inhibition of the transcription factor NF-kappa B besides affecting several biological pathways to arrest tumor growth and its progression. Curcumin with all these positive qualities has only remained a potential candidate for cancer treatment over the years without seeing any proper usage because of its hydrolytic instability involving the diketo moiety in a cellular medium and its poor bioavailability. The situation has changed considerably in recent years with the observation that curcumin in monoanionic form could be stabilized on binding to a metal ion. The reports from our group and other groups have shown that curcumin in the metal-bound form retains its therapeutic potential. This has opened up new avenues to develop curcumin-based metal complexes as anticancer agents. Zinc(II) complexes of curcumin are shown to be stable in a cellular medium. They display moderate cytotoxicity against prostate cancer and neuroblastoma cell lines. A similar stabilization and cytotoxic effect is reported for (arene)ruthenium(II) complexes of curcumin against a variety of cell lines. The half-sandwich 1,3,5-triaza-7-phosphatricyclo-3.3.1.1]decane (RAPTA)-type ruthenium(II) complexes of curcumin are shown to be promising cytotoxic agents with low micromolar concentrations for a series of cancer cell lines. In a different approach, cobalt(III) complexes of curcumin are used for its cellular delivery in hypoxic tumor cells using intracellular agents that reduce the metal and release curcumin as a cytotoxin. Utilizing the photophysical and photochemical properties of the curcumin dye, we have designed and synthesized photoactive curcumin metal complexes that are used for cellular imaging by fluorescence microscopy and damaging the cancer cells on photoactivation in visible light while being minimally toxic in darkness. In this Account, we have made an attempt to review the current status of the chemistry of metal curcumin complexes and present results from our recent studies on curcumin complexes showing remarkable in vitro photocytotoxicity. The undesirable dark toxicity of the complexes can be reduced with suitable choice of the metal and the ancillary ligands in a ternary structure. The complexes can be directed to specific subcellular organelles. Selectivity by targeting cancer cells over normal cells can be achieved with suitable ligand design. We expect that this methodology is likely to provide an impetus toward developing curcumin-based photochemotherapeutics for anticancer treatment and cure.

Control of Variable Watermilfoil in Bashan Lake, CT with 2,4-D: Monitoring of Lake and Well Water.

Variable watermilfoil (Myriophyllum heterophyllum Michx.) has recently become a problem in Bashan Lake, East Haddam, CT, USA. By 1998, approximately 4 ha of the 110 ha lake was covered with variable watermilfoil. In 1999, the milfoil was spot treated with Aquacide®, an 18% active ingredient of the sodium salt of 2,4-D [(2,4-dichlorophenoxy) acetic acid], applied at a rate of 114 kg/ha. Aquacide® was used because labeling regarding domestic water intakes and irrigation limitations prevented the use of Navigate® or AquaKleen®, a 19% active ingredient of the butoxyethyl ester of 2,4-D. Variable watermilfoil was partially controlled in shallow protected coves but little control occurred in deeper more exposed locations. 2,4-D levels in the treatment sites were lower than desired and offsite dilution was rapid. In 2000, the United States Environmental Protection Agency (USEPA) issued a special local need (SLN) registration to allow the use of Navigate ® or AquaKleen® in lakes with potable and irrigation water intakes. Navigate® was applied at a rate of 227 kg/ha to the same areas as treated in 1999. An additional 2 ha of variable watermilfoil was treated with Navigate® in 2001, and 0.4 ha was treated in mid-September. Dilution of the 2,4-D ester formulation to untreated areas was slower than with the salt formulation. Concentrations of 2,4-D exceeded 1000 μg/ L in several lake water samples in 2000 but not 2001. Nearly all of the treated variable watermilfoil was controlled in both years. The mid-September treatment appeared as effective as the spring and early summer treatments. Testing of homeowner wells in all 3 years found no detectable levels of 2,4-D.(PDF contains 8 pages.)

Endothall species selectivity evaluation: northern latitude aquatic plant community

Species selectivity of the aquatic herbicide dipotassium salt of endothall (Aquathol® K) was evaluated on plant species typically found in northern latitude aquatic plant communities. Submersed species included Eurasian watermilfoil (Myriophyllum spicatum L.), curlyleaf pondweed (Potamogeton crispus L.), Illinois pondweed (Potamogeton illinoensis Morong.), sago pondweed (Potamogeton pectinatus L.), coontail (Ceratophyllum demersum L.), elodea (Elodea canadensis Michx.) and wildcelery (Vallisneria americana L.). Emergent and floating-leaf plant species evaluated were cattail (Typha latifolia L.), smartweed (Polygonum hydropiperoides Michx.), pickerelweed (Pontederia cordata L.) and spatterdock (Nuphar advena Aiton). The submersed species evaluations were conducted in 7000 L mesocosm tanks, and treatment rates included 0, 0.5 1.0, 2.0, and 4.0 mg/L active ingredient (ai) endothall (dipotassium salt of endothall). The exposure period consisted of a 24-h flow through half-life for 7 d. The cattail and smartweed evaluation was conducted in 860 L mesocosm tanks, and the spatterdock and pickerelweed evaluations were conducted in 1600 L mesocosm tanks. Treatment rates for the emergent and floating-leafed plant evaluations included 0, 0.5, 2.0 and 4.0 mg/L ai endothall, and the exposure period consisted of removing and replacing half the water from each tank, after each 24 h period for a duration of 120 h. Biomass samples were collected at 3 and 8 weeks after treatment (WAT). Endothall effectively controlled Eurasian watermilfoil and curlyleaf pondweed at all of the application rates, and no significant regrowth was observed at 8 WAT. Sago pondweed, wildcelery, and Illinois pondweed biomass were also significantly reduced following the endothall application, but regrowth was observed at 8 WAT. Coontail and elodea showed no effects from endothall application at the 0.5, 1.0, and 2.0 mg/L application rates, but coontail was controlled at 4.0 mg/L rate. Spatterdock, pickerelweed, cattail, and smartweed were not injured at any of the endothall application rates.

Impacts of inorganic turbidity on diquat efficacy against Egeria densa

In clear water, diquat [6,7-dihydrodipyrido (1,2-1a:2',1'-c) pyrazinediium dibromide] provides excellent submersed Plant control at low concentrations, such as <0.5 mg active ingredient (ai) L-1: however. turbid water conditions can interfere with the activity and effectiveness of this herbicide. Little work has been done to examine what ranges of turbidity caused by different Suspended sediment types affect diquat efficacy against a target species. A growth chamber study was conducted rising diquat against the submersed macrophyte -egeria (Egeria densa Planch.) under a range Of turbid conditions. Two materials were used to create turbid beater conditions: 100% bentonite clay for a "worst-case" scenario and a natural partial-clav (20% clay). Results indicated that a high rate of diquat (2 mg ai L-1) controlled egeria under relatively low levels of turbidity (5-10 NTU) using bentonite clay: however. higher levels (25 to 50 NTU) of turbidity essentially blocked effectiveness of diquat when applied at all rates tested (0.5. 1, 2 mg ai L-1). When using a natural partial-clay sediment, rates of 1 to 2 mg ai L-1 diquat provided good control of egeria in moderately turbid water (15 NTU). Additional evaluations rising different clay types would be useful to determine the effect of inorganic turbidity oil diquat efficacy.

The Impact of Endothall on the Aquatic Plant Community of Kress Lake, Washington

CA dense mat-forming population of Eurasian watermilfoil ( Myriophyllum spicatum L . ) was interfering with fishing and recreation in a small western Washington lake. A low concentration (1.5 mg/L active ingredient) of the herbicide endothall formulated as Aquathol® K was used in 2000 to attempt to selectively control the Eurasian watermilfoil. Aquatic plant biomass and frequency data were collected before treatment, ten weeks after treatment and during the growing season for 3 additional years. Macrophyte data were analyzed to assess the herbicide’s impacts on Eurasian watermilfoil as well as the rest of the aquatic plant community. Results showed a significant decrease in Eurasian watermilfoil biomass and frequency 10 weeks after treatment. The Eurasian watermilfoil continued to be present, but at a significantly reduced level through the remainder of the study (3 years after treatment). Of the native plant species, large-leaf pondweed ( Potamogeton amplifolius Tucker . ) frequency and biomass was significantly reduced after treatment. Common elodea ( Elodea canadensis Rich.), muskgrass ( Chara sp. Vallaint.) and bladderwort ( Utricularia sp. L.) all increased significantly after treatment. (PDF has 6 pages.)

Aplicação de processos com membranas na remoção de piretróides de efluentes industriais

O tratamento de efluentes industriais tem sido objeto de estudos no sentido da busca de soluções que minimizem impactos ambientais e promovam a conservação do bem natural que é a água. Nesta linha de pensamento, o presente trabalho propôs-se avaliar a viabilidade de recuperação de efluentes industriais contaminados com pesticidas do tipo piretróides em específico: a deltametrina e beta-ciflutrina. A justificativa na escolha deste tipo de componente está fundamentada na alta demanda alimentícia por parte da população mundial e o consequente acréscimo no uso dos agrotóxicos a fim de garantir a eficiência e o elevado volume de produção de alimentos. O objetivo deste trabalho foi estudar a remoção da deltametrina e da beta-ciflutrina de efluentes sintéticos aquosos por meio dos processos de osmose inversa e nanofiltração, com a utilização de membranas de poliamida. O presente estudo se justifica pelo atendimento aos padrões ambientais de concentração de piretróides no meio ambiente e reafirma o uso do sistema com membranas no tratamento de efluentes e remoção destes contaminantes. Para caracterização das membranas, foi realizado o teste de permeabilidade hidráulica, constatando diferentes linearidades de fluxo entre os dois processos, com a variação de pressão de trabalho. O desempenho dos processos foi verificado pela variação de parâmetros de meio reacional, variando a concentração dos piretróides em solução, analisando os princípios ativos isolados e também em mistura de ambos piretróides. Primeiramente se estudou a remoção da deltametrina e da beta-ciflutrina isoladamente em solução, nas concentrações de 5, 25, 50 e 100 mg L-1, sob a pressão de 5 bar. Posteriormente, avaliou-se o desempenho das membranas na remoção dos piretróides em mistura nas soluções sintéticas, com ambos os princípios ativos na concentração de 50 mg L-1, na pressão de 5 bar. Foi estudada a remoção da deltametrina e da beta-ciflutrina nos dois processos: osmose inversa e nanofiltração. Os resultados foram tratados estatisticamente por análise de variância (ANOVA) e pela análise por comparação de amostras independentes a fim de verificar a significância dos valores obtidos e a influência da variação dos parâmetros analisados. Para a faixa de concentração estudada (5, 25, 50 e 100 mg L-1) os valores encontrados de concentração de permeado foram todos consideravelmente baixos. O maior valor encontrado foi de 0,026 mg L-1 no ensaio de nanofiltração com concentração inicial de 5 mg L-1 de beta-ciflutrina em água. Os resultados apresentaram excelentes rejeições em todos os testes, seja com princípio ativo isolado ou em mistura, com rejeições maiores que 99,5% para ambos os piretróides nas concentrações testadas, sob a pressão de 5 bar. O processo de nanofiltração apresentou maiores e melhores fluxos de permeado do que a osmose inversa. Contudo, no que diz respeito à eficácia da separação, ambos processos indicaram ótimo desempenho na remoção dos piretróides, viabilizando assim, a escolha destes métodos para tratamento de efluentes contaminados com este pesticida

Efecto del glifosato en la morfologia del tubo dogestivo y en la actividad acetilcolinesterasa de la lombriz Eisenia fetida

[EUS] Gaur egun produktu kimiko ugari erabiltzen dira nekazaritzaren produktibitatea emendatzeko eta modu honetan nekazaritza-produktuen etekin eta kalitatea hobetzeko asmoz. Hala ere, produktu kimiko hauek ekosisteman izan ditzaketen hilgarriak ez diren eraginak askotan ez dira kontuan hartzen. Azken urteotan osagai aktibo gisa glifosatoa duten herbiziden erabilera emendatu da. Lan honetan, glifosatoak ingurunean sor ditzakeen eraginak ikertu nahi izan dira, lurzoruan oso ugaria den Eisenia fetida zizarea adierazle biologiko gisa erabiliz. Esperimentuan 10 indibiduo helduz osaturiko 4 populazio erabili ziren, zeinak 14 egunez tratamendu desberdinetan ezarri ziren (kontrola, 50, 500 eta 5000 mg glifosato/Kg lur lehor). Glifosato kontzentrazio desberdinek ez zuten zizareen hilkortasunean edo pisuaren aldaketan eraginik izan. Hala ere, digestio-hodiaren epitelioaren morfologian eta azetilkolinesterasaren jardueran aldaketak behatu ziren. Glifosato kontzentrazio baxueneko ontziko zizareetan digestio-hodiko epitelioaren altueraren uniformetasun falta behatu zen, glifosato kontzentrazio ertaineko ontziko zizareetan orokorrean epitelioaren altuera txikiagoa zen, eta glifosato kontzentrazio handieneko ontziko zizareetan digestio-hodien borobiltasuna eta epitelioaren jarraitasuna galdu zen. Azetilkolinesterasaren jardueraren murrizpena behatu zen glifosatodun lurretan egondako zizareetan. Esperimentu honetan erabilitako glifosato kontzentrazioek zizareengan hilgarriak ez diren aldaketak sortzen dituzte, aztertutako biomarkatzaileak etorkizuneko ekotoxikologia testetan erabilgarriak izan daitezkeelarik.

Avaliação da exposição de botos-cinza (Sotalia guianensis Van Benédén, 1864) aos compostos orgânicos de estanho através das concentrações hepáticas de estanho total na costa sudeste e sul do Brasil

Durante as últimas décadas, observou-se um aumento da preocupação em relação aos ecossistemas marinhos devido à grande entrada de poluentes, resultando em efeitos deletérios em organismos aquáticos e seres humanos. Dentre as atividades humanas que podem introduzir compostos tóxicos persistentes e bioacumulativos (PBTs Persistent Bioaccumulative Toxicants) no ambiente marinho está o uso de tintas antiincrustrantes, aplicadas nos cascos de navios para evitar que algas, mexilhões e outros organismos se fixem às embarcações. Não raramente, compostos organoestânicos (OTs) como o Tributilestanho (TBT) ou o Trifenilestanho (TPT) constituíam o princípio ativo de tal preparado. Devido à alta toxicidade desses compostos, a IMO (Organização Marítima Internacional) baniu totalmente o uso dos mesmos. Como os OTs são prontamente bioacumulados, elevadas concentrações de estanho total (SnT) vêm sendo encontradas em cetáceos (Mammalia, Cetacea). Os botos-cinza (Sotalia guianensis Van Beneden, 1864) ocupam elevados níveis tróficos e bioacumulam os PBTs aos quais estão expostos. Alguns autores relataram que o estanho hepático em cetáceos se encontra predominantemente na forma orgânica, visto que, na forma inorgânica tal metal é pobremente absorvido pela mucosa gastrintestinal, de forma que as concentrações hepáticas de SnT refletem o input antrópico de OTs. O presente estudo teve como principal objetivo, avaliar a exposição de botos-cinza aos OTs, através determinação das concentrações hepáticas de estanho total (SnT = orgânico + inorgânico), por Espectrometria de Absorção Atômica com Atomização em Forno de Grafite (GFAAS Graphite Furnace Atomic Absorption Spectrometry). Para tal, amostras de botos-cinza de diferentes áreas do litoral brasileiro, compreendendo a Região da Grande Vitória (GV), Baía de Guanabara (BG), Baía de Sepetiba (B.Sep), a Baía de Paranaguá (PR) e a Baía da Babitonga (SC), foram analisadas, visando comparar ambientes distintamente contaminados com OTs. Sendo assim, as concentrações hepáticas de SnT (em ng/g, peso seco) de botos-cinza variaram de <312 (limite de detecção) a 8.250, para a GV (n=22); de <312 a 14.100, para B.Sep (n = 38); <312 a 5.147, para PR (n= 22), bem como de 626 a 24.780 (ng/g, peso seco) para os botos de SC (n=10). As maiores concentrações foram verificadas nos botos da BG (n=11), variando de 1.265 a 24.882 (ng/g, peso seco). As concentrações encontradas na Baía de Guanabara (BG) estão entre as mais elevadas detectadas em cetáceos.

The cost of quinine Cinchona pubescens control on Santa Cruz Island, Galapagos

We analyse the cost of controlling the invasive quinine tree Cinchona pubescens Vahl in the highlands of Santa Cruz Island, Galapagos. Control costs in ten 400 m2 plots formed the basis for estimating the cost of control over the whole island. In the plots, densities were 2100–24,000 stems/ha (stems >150 cm tall) and 55,000–138,000 stems/ha (all size classes combined). Control involved uprooting small plants, and applying of a mix of metsulfuron methyl and picloram to cut stumps or to machete cuts in the bark of larger trees. These methods are presently used by Galapagos National Park field crews to control quinine. Costs (in man hours, herbicide and US$) were related to stem density; the density of stems summed across four height classes was a better predictor of costs than density of any one size class. Regressions (on all size classes combined) formed the basis for predictive models of costs. Costs ranged from $14 to $2225 per ha depending on stem density. The amount of herbicide (active ingredient/ha) that must be applied to high density stands of quinine is higher than typical rates of application in an agricultural setting. The cost of treating all existing plants once across quinine’s known range on Santa Cruz Island (c. 11,000 ha) was estimated at c. US$1.65 million. CDF Contribution Number 1013.

Evaluation of quality of shark livers using bio-chemical properties and organoleptic score sheet

Shark livers are considered as an important raw material providing a quality fish oil. It has been reported to aid white — blood-cell production and act as an active ingredient in hemorrhoid treatments. It is also reported that liver oil as a good supplement of vitamin A and poly-unsaturated fatty acids which are important to the development of brain cells in human. Freshness of livers is very important to extract better quality oil. In Sri Lanka, the annual shark production amounts to 8000t, however the quality of livers collected from landing sites has not being measured yet. Present study was conducted to evaluate the quality of silky (Charcarninus fakiformis) shark livers available in Negombo and Beruwala landing sites in the West Coast of Sri Lanka and also to study the relationship between organoleptic and bio-chemical correlation on freshness of shark livers. Liver samples which were collected from landing sites in the West coast of Sri Lanka, were evaluated for external and internal colour, texture and odour. Total volatile nitrogen (TVN), pH value, free fatty acid (FFA%) and peroxide (PV) values of livers were also determined to assess quality. According to the organoleptic scoring system 4.3% of liver samples were categorized as best in quality while 30.4%, 56.5% and 8.7% rated as good, medium and poor in quality respectively at the Negombo and Beruwala landing sites. Bio-chemical analysis showed that the better quality livers had the highest score for sensory evaluation and low values for TVN, FFA and peroxide value while low quality livers gave low score for sensory evaluation and high TVN, FFA, peroxide values. Correlation coefficient of organoleptic scores against total volatile nitrogen value, pH value, free fatty acid % and peroxide value of shark livers were determined by statistical analysis. Organoleptic score of shark livers was found to be highly.

氮、磷、钾对膜荚黄芪生长发育及有效成分的影响

目的:研究氮、磷、钾及其配比对膜荚黄芪生长发育及有效成分的影响。方法:通过田间试验,采用氮、磷、钾3因素2次D-饱和最优设计,研究氮、磷、钾及其配比对膜荚黄芪生长及有效成分的影响。结果:施肥促进了膜荚黄芪幼苗的生长,从而为生育后期膜荚黄芪根生长、产量形成及有效成分的累积提供充足的营养基础。氮、磷、钾各元素及其配比明显促进了茎叶及根干物质积累,氮、磷、钾对膜荚黄芪干物质累积总量的影响程度依次为氮>钾>磷;对膜荚黄芪茎叶干物质累积量的影响程度依次为氮>磷>钾;对根干物质累积量的影响程度依次为氮>钾>磷。施肥明显提高了膜荚黄芪根产量,氮、磷、钾对根产量影响程度依次为氮>钾>磷。氮、磷、钾各元素及其配比使黄芪多糖、黄芪甲苷含量明显增加,对总黄酮含量影响不明显。氮、磷、钾对黄芪多糖含量影响程度依次为钾>磷>氮;对黄芪甲苷含量的影响程度依次为氮>钾>磷。结论:氮、钾对膜荚黄芪生长发育,产量形成及多糖,黄芪甲苷含量有重要的影响。根类中药材黄芪的栽培过程中应该注重氮、钾肥的施用,并注意氮、磷、钾的配合施用。

Determination of benzhexol hydrochloride by capillary zone electrophoresis with an end-column electrochemiluminescence detection

A capillary zone electrophoresis with end-column electrochemiluminescence (ECL) detector was described for the determination of benzhexol hydrochloride. The detection was based on the tris(2,2'-bypyridine)ruthenium(II) [Ru(bpy)(3)(2+)] ECL reaction with the analyte. Electrophoresis was performed using a 25 mum i.d. uncoated capillary. 10 mM sodium phosphate buffer (pH=8.0) was used as the running buffer. The solution in the detection cell was 80 mM sodium phosphate (pH=8.0) and 5 mM)21 Ru(bpy)(3)(2+). A linear calibration curve of three-orders of magnitude was obtained (with a correlation coefficient of > 0.999) from 1.0X10(-8) to 1.0X10(-5) M and the limit of detection was 6.7 X 10(-9) M (S/N= 3). This just provides an easy and sensitive method to determine the active ingredient in pharmaceutical formulations.

Selección de un aislado del nucleopoliedrovirus de Helicoverpa armigera (HearNPV) para su uso como base de un bioinsecticida

Helicoverpa armigera (Lepidoptera; Noctuidae), conocida como el taladro del tomate, es una especie polífaga y de amplia distribución, responsable de grandes pérdidas económicas en más de 60 cultivos a lo largo de las regiones tropicales y subtropicales del mundo. Estas plagas se controlan mayoritariamente con plaguicidas químicos, aunque existe un gran interés por desarrollar otros agentes de control biológico. Entre estos, se encuentra el nucleopoliedrovirus de Helicoverpa armigera (HearNPV, Baculoviridae), que por sus características de seguridad y eficacia, sería útil para impulsar los programas de gestión integrada de plagas que se fomentan desde la Directiva 2009/128/CEE. El objetivo de este trabajo fue realizar una caracterización bioquímica y biológica de varios aislados de HearNPV : un aislado silvestre español (Badajoz) HearNPV-SP1, un aislado chino HearSNPV-G4, tres aislados sudafricanos (HearNPV-Whl, HearNPV-Kzn, HearNPV-Alb) y la materia activa de un producto comercial en uso en Europa (HearNPV-Hx). El análisis con las enzimas de restricción determinó que la enzima BglII generaba perfiles similares pero con fragmentos característicos en todos los casos a excepción de los aislados HearNPV-Kzn y HearNPVAlb, que no pudieron ser diferenciados entre sí con ninguna de las enzimas probadas. El análisis filogenético, basado en las secuencias parciales de los genes poliedrina (polh), lef-8 y lef-9, donde se incluyeron las secuencias correspondientes a 18 genomas mostró que el aislado HearNPV-Whl es filogenéticamente próximo a las cepas de origen ibérico, mientras que los aislados HearNPV-Hx y HearNPV-Alb comparten la misma rama que los aislados asiáticos y australiano. La caracterización insecticida de los aislados HearNPV-SP1, HearNPV-Hx y HearNPV-G4 reveló que la virulencia (TMM) del aislado HearNPV-SP1 (104 h) fue significativamente menor que la de los aislados HearNPV-G4 (109 h) y HearNPV-Hx (111 h). En este trabajo, se determinó que el tiempo de acción del HearNPV-SP1 es menor al de otros bioinsecticidas en uso en Europa, por lo que se confirma la posibilidad de mejorar los productos activos en uno de los aspectos más sensibles de cara a su comercialización como es su tiempo de actuación.

Fitocompostos com atividade antineoplásica – paclitaxel e seus derivados

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas

A review of glaucoma treatment in Scotland 1994-2004

Objective: This study evaluated the changing trends in glaucoma management in Scotland between 1994 and 2004. Methods: A retrospective analysis of national health statistics in Scotland from 1994 to 2004. The Scottish morbidity record was used to collect information on all episodes of trabeculectomy. Data on number of prescriptions were gathered for individual drugs and also for groups of active ingredient. The population likely to have glaucoma (PLG) was calculated from estimates of prevalence in individuals aged 40 years and older, based on published epidemiological studies. The outcome measures were trabeculectomy rates, corrected for population likely to be at risk of glaucoma (PLG), and prescribing volume and cost for glaucoma medications. Results: Trabeculectomy rates have fallen by 67% from 46 per 1000 PLG in 1994 to 15.4 per 1000 PLG in 2004. Over the same time period, the population likely to be at risk of glaucoma (PLG) increased by 16.6%. The cost of prescribing has increased by 122% over 11 years compared with an increase in number of items per 1000 PLG by 27.5%. In 1994, ß-blockers accounted for 65.2% of prescribed drugs but by 2004 this had dropped to 33%. Since their introduction, the prescribing of prostaglandin analogues has increased rapidly and in 2004, they accounted for 39.4% of prescribed drugs. Conclusion: The increasing useof prostaglandin analogues has led to an increase in prescribing rates and a rapid increase in cost. At the same time, prescribing of ß-blockers has declined and trabeculectomy rates have fallen.