SummaryAbstractPioglitazone is an antihyperglycaemic agent that, in the presence of insulin resis... more SummaryAbstractPioglitazone is an antihyperglycaemic agent that, in the presence of insulin resistance, increases hepatic and peripheral insulin sensitivity, thereby inhibiting hepatic gluconeogenesis and increasing peripheral and splanchnic glucose uptakePioglitazone is generally well tolerated, weight gain and oedema are the most common emergent adverse events, and there are no known drug interactions between pioglitazone and other drugs. In clinical trials in patients with type 2 diabetes mellitus, pioglitazone as monotherapy, or in combination with metformin, repaglinide, insulin or a sulfonylurea, induced both long- and short-term improvements in glycaemic control and serum lipid profiles. Pioglitazone was also effective in reducing some measures of cardiovascular risk and arteriosclerosis. Pioglitazone thus offers an effective treatment option for the management of patients with type 2 diabetes.Pharmacological PropertiesPioglitazone activates a specific nuclear receptor, the peroxisome-proliferator activated receptor-γ, which increases insulin sensitivity in liver, fat and skeletal muscle cells, increases peripheral and splanchnic glucose uptake and decreases hepatic glucose output. Pioglitazone is dependent on the presence of insulin in order to exert its beneficial effects and may help preserve β-cells of the islets of Langerhans, but does not act as an insulin secretagogue.Pioglitazone promotes lipid storage and redistribution from visceral to subcutaneous deposits, resulting in an increase in whole body adiposity, while promoting the differentiation of adipocytes. It also appears to have protective effects against atherosclerosis and antihypertensive actions.Following oral administration of pioglitazone in patients with type 2 diabetes, peak plasma concentrations of pioglitazone are achieved in 2–2.5 hours. Plasma concentrations are dose dependent and steady state is achieved after 4–7 days’ treatment. Bioavailability is 83% and there is no accumulation of pioglitazone or its metabolites after repeated administration. Pioglitazone is metabolised in the liver predominantly via the cytochrome P450 enzyme system. About 15–30% of a dose is renally excreted, mainly as metabolites and their conjugates, with the remainder eliminated in faeces.Therapeutic EfficacyIn well designed, randomised, controlled monotherapy trials of up to 2 years’ duration in patients with type 2 diabetes, glycaemic control improved with pioglitazone 15, 30 or 45 mg/day versus baseline and placebo. Improvements in glycaemic control in pioglitazone recipients were similar to those of metformin, insulin and rosiglitazone recipients, and greater than those in recipients of acar-bose or the sulfonylureas gliclazide, glimepiride or glibenclamide.Additive effects on glycaemic profiles occurred when pioglitazone was used in combination with metformin, repaglinide, insulin or the sulfonylureas gliclazide, glipizide, glimepiride or glibenclamide (glyburide).In patients with type 2 diabetes, lipid control was also improved with pioglitazone versus baseline and placebo in monotherapy trials and in trials in combination with metformin, insulin and sulfonylureas. Furthermore pioglitazone produced greater reductions in serum triglycerides and greater increases in high-density lipoprotein-cholesterol than metformin, sulfonylureas or rosiglitazone.Pioglitazone also reduced a cardiovascular risk parameter (carotid intima-media thickness), inflammatory biomarkers of arteriosclerosis (high sensitivity C-reactive protein, matrix metalloproteinase and monocyte chemoattractant protein levels) and a secondary composite measure of the risk of macrovascular events (all-cause mortality, nonfatal myocardial infarct, stroke), but not the primary composite endpoint (all-cause mortality, nonfatal myocardial infarct [MI] including silent MI, stroke, major leg amputation, acute coronary syndrome, cardiac intervention or leg revascularisation).TolerabilityPioglitazone was generally well tolerated in patients with type 2 diabetes in clinical trials of up to 2.5 years’ duration when used as monotherapy and in combination with other drugs including metformin, a sulfonylurea, repaglinide or insulin. The most commonly reported treatment-emergent adverse events were weight gain, oedema, arthralgia, headache and decreases in haemoglobin and haematocrit levels.Hepatocellular dysfunction and of hepatic enzyme elevations of three or more times the upper limit of normal have rarely been reported, and very rarely have involved hepatic failure with and without fatal outcome, although a causal link has not been established. Overall, small reductions in mean liver enzyme levels with pioglitazone treatment have been observed.
List of all sequences of a standardised 648â bp region of the cytochrome c oxidase gene obtained ... more List of all sequences of a standardised 648â bp region of the cytochrome c oxidase gene obtained from New Zealand and closely related bird species used in this study including Genbank accession numbers. (DOCX 63 kb)
The use of DNA barcodes (haplotypic variation in a 648 bp segment of the cytochrome c oxidase sub... more The use of DNA barcodes (haplotypic variation in a 648 bp segment of the cytochrome c oxidase subunit I [COI] gene within the mitochondrial genome, starting from base 58 at the 5’ end of the gene) as part of a species description is an accepted part of modern taxonomy. The evidence COI provides is compelling since a sequence of DNA is biological data obtained from living material. Early in the use of COI, it became apparent that it might highlight potential cryptic species and inform the debate around their status. The little penguin (Eudyptula minor) has been the subject of such debate. DNA barcodes from 60 little penguins were assessed to determine the specific status of this species across its range. Analysis of these data indicates distinct Australian and New Zealand haplotypes that may be indicative of separation at the species level. The specific status for the 2 populations is also supported by behavioural evidence and geographic isolation. Waugh, J. 2016. DNA barcodes highli...
Neighbour Joining tree of sequences of a standardised 648â bp region of the cytochrome c oxidase ... more Neighbour Joining tree of sequences of a standardised 648â bp region of the cytochrome c oxidase gene obtained from New Zealand and closely related bird species in this study. Bootstrap support values â Ľ0.5 are indicated. Monophyletic clades have been collapsed. Branches are coloured by Order. (PDF 6097 kb)
Cumulative error plot of type I (false positive) and type II (false negative) errors for differen... more Cumulative error plot of type I (false positive) and type II (false negative) errors for different divergence thresholds of maximum intraspecific and minimum interspecific genetic distances measured using a standardised 648â bp region of the cytochrome c oxidase gene for all New Zealand bird species with >â 1 specimen obtained during the study. The optimal threshold occurs at 0.25%. (DOCX 171 kb)
Despite 250 years of work in systematics, the majority of species remains to be identified. Risin... more Despite 250 years of work in systematics, the majority of species remains to be identified. Rising extinction rates and the need for increased biological monitoring lend urgency to this task. DNA sequencing, with key sequences serving as a "barcode", has therefore been proposed as a technology that might expedite species identification. In particular, the mitochondrial cytochrome c oxidase subunit 1 gene has been employed as a possible DNA marker for species and a number of studies in a variety of taxa have accordingly been carried out to examine its efficacy. In general, these studies demonstrate that DNA barcoding resolves most species, although some taxa have proved intractable. In some studies, barcoding provided a means of highlighting potential cryptic, synonymous or extinct species as well as matching adults with immature specimens. Higher taxa, however, have not been resolved as accurately as species. Nonetheless, DNA barcoding appears to offer a means of identifying species and may become a standard tool.
Pioglitazone is an antihyperglycaemic agent that, in the presence of insulin resistance, increase... more Pioglitazone is an antihyperglycaemic agent that, in the presence of insulin resistance, increases hepatic and peripheral insulin sensitivity, thereby inhibiting hepatic gluconeogenesis and increasing peripheral and splanchnic glucose uptake. Pioglitazone is generally well tolerated, weight gain and oedema are the most common emergent adverse events, and there are no known drug interactions between pioglitazone and other drugs. In clinical trials in patients with type 2 diabetes mellitus, pioglitazone as monotherapy, or in combination with metformin, repaglinide, insulin or a sulphonylurea, induced both long- and short-term improvements in glycaemic control and serum lipid profiles. Pioglitazone was also effective in reducing some measures of cardiovascular risk and arteriosclerosis. Pioglitazone thus offers an effective treatment option for the management of patients with type 2 diabetes.
Sources: medical literature published in any language since 1997 on adapalene, identified using M... more Sources: medical literature published in any language since 1997 on adapalene, identified using Medline and EMBASE, supplemented by AdisBase (a proprietary database of Adis International). Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug. Search strategy: Medline search terms were 'adapalene' or 'CD-271'. EMBASE search terms were 'adapalene' or 'CD 271'. AdisBase search terms were 'adapalene' or 'CD271'. Searches were last updated 10 May 2004. Selection: Studies in patients with acne vulgaris who received adapalene. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.
BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy, 2005
Anakinra (Kineret) is the first biologic drug that has been developed specifically as an interleu... more Anakinra (Kineret) is the first biologic drug that has been developed specifically as an interleukin (IL)-1 receptor antagonist (Ra) and is derived from an endogenous IL-1Ra. The drug blocks the activity of IL-1 in synovial joints, reducing the inflammatory and joint destructive processes associated with rheumatoid arthritis (RA). In randomized, placebo-controlled trials of up to 52 weeks' duration, anakinra has shown efficacy both as monotherapy and in combination with other disease-modifying antirheumatic drugs (DMARDs) in adults with RA. It is subcutaneously administered and is generally well tolerated. Anakinra offers a useful addition to the range of drugs available for the treatment of RA.
SummaryAbstractPioglitazone is an antihyperglycaemic agent that, in the presence of insulin resis... more SummaryAbstractPioglitazone is an antihyperglycaemic agent that, in the presence of insulin resistance, increases hepatic and peripheral insulin sensitivity, thereby inhibiting hepatic gluconeogenesis and increasing peripheral and splanchnic glucose uptakePioglitazone is generally well tolerated, weight gain and oedema are the most common emergent adverse events, and there are no known drug interactions between pioglitazone and other drugs. In clinical trials in patients with type 2 diabetes mellitus, pioglitazone as monotherapy, or in combination with metformin, repaglinide, insulin or a sulfonylurea, induced both long- and short-term improvements in glycaemic control and serum lipid profiles. Pioglitazone was also effective in reducing some measures of cardiovascular risk and arteriosclerosis. Pioglitazone thus offers an effective treatment option for the management of patients with type 2 diabetes.Pharmacological PropertiesPioglitazone activates a specific nuclear receptor, the peroxisome-proliferator activated receptor-γ, which increases insulin sensitivity in liver, fat and skeletal muscle cells, increases peripheral and splanchnic glucose uptake and decreases hepatic glucose output. Pioglitazone is dependent on the presence of insulin in order to exert its beneficial effects and may help preserve β-cells of the islets of Langerhans, but does not act as an insulin secretagogue.Pioglitazone promotes lipid storage and redistribution from visceral to subcutaneous deposits, resulting in an increase in whole body adiposity, while promoting the differentiation of adipocytes. It also appears to have protective effects against atherosclerosis and antihypertensive actions.Following oral administration of pioglitazone in patients with type 2 diabetes, peak plasma concentrations of pioglitazone are achieved in 2–2.5 hours. Plasma concentrations are dose dependent and steady state is achieved after 4–7 days’ treatment. Bioavailability is 83% and there is no accumulation of pioglitazone or its metabolites after repeated administration. Pioglitazone is metabolised in the liver predominantly via the cytochrome P450 enzyme system. About 15–30% of a dose is renally excreted, mainly as metabolites and their conjugates, with the remainder eliminated in faeces.Therapeutic EfficacyIn well designed, randomised, controlled monotherapy trials of up to 2 years’ duration in patients with type 2 diabetes, glycaemic control improved with pioglitazone 15, 30 or 45 mg/day versus baseline and placebo. Improvements in glycaemic control in pioglitazone recipients were similar to those of metformin, insulin and rosiglitazone recipients, and greater than those in recipients of acar-bose or the sulfonylureas gliclazide, glimepiride or glibenclamide.Additive effects on glycaemic profiles occurred when pioglitazone was used in combination with metformin, repaglinide, insulin or the sulfonylureas gliclazide, glipizide, glimepiride or glibenclamide (glyburide).In patients with type 2 diabetes, lipid control was also improved with pioglitazone versus baseline and placebo in monotherapy trials and in trials in combination with metformin, insulin and sulfonylureas. Furthermore pioglitazone produced greater reductions in serum triglycerides and greater increases in high-density lipoprotein-cholesterol than metformin, sulfonylureas or rosiglitazone.Pioglitazone also reduced a cardiovascular risk parameter (carotid intima-media thickness), inflammatory biomarkers of arteriosclerosis (high sensitivity C-reactive protein, matrix metalloproteinase and monocyte chemoattractant protein levels) and a secondary composite measure of the risk of macrovascular events (all-cause mortality, nonfatal myocardial infarct, stroke), but not the primary composite endpoint (all-cause mortality, nonfatal myocardial infarct [MI] including silent MI, stroke, major leg amputation, acute coronary syndrome, cardiac intervention or leg revascularisation).TolerabilityPioglitazone was generally well tolerated in patients with type 2 diabetes in clinical trials of up to 2.5 years’ duration when used as monotherapy and in combination with other drugs including metformin, a sulfonylurea, repaglinide or insulin. The most commonly reported treatment-emergent adverse events were weight gain, oedema, arthralgia, headache and decreases in haemoglobin and haematocrit levels.Hepatocellular dysfunction and of hepatic enzyme elevations of three or more times the upper limit of normal have rarely been reported, and very rarely have involved hepatic failure with and without fatal outcome, although a causal link has not been established. Overall, small reductions in mean liver enzyme levels with pioglitazone treatment have been observed.
List of all sequences of a standardised 648â bp region of the cytochrome c oxidase gene obtained ... more List of all sequences of a standardised 648â bp region of the cytochrome c oxidase gene obtained from New Zealand and closely related bird species used in this study including Genbank accession numbers. (DOCX 63 kb)
The use of DNA barcodes (haplotypic variation in a 648 bp segment of the cytochrome c oxidase sub... more The use of DNA barcodes (haplotypic variation in a 648 bp segment of the cytochrome c oxidase subunit I [COI] gene within the mitochondrial genome, starting from base 58 at the 5’ end of the gene) as part of a species description is an accepted part of modern taxonomy. The evidence COI provides is compelling since a sequence of DNA is biological data obtained from living material. Early in the use of COI, it became apparent that it might highlight potential cryptic species and inform the debate around their status. The little penguin (Eudyptula minor) has been the subject of such debate. DNA barcodes from 60 little penguins were assessed to determine the specific status of this species across its range. Analysis of these data indicates distinct Australian and New Zealand haplotypes that may be indicative of separation at the species level. The specific status for the 2 populations is also supported by behavioural evidence and geographic isolation. Waugh, J. 2016. DNA barcodes highli...
Neighbour Joining tree of sequences of a standardised 648â bp region of the cytochrome c oxidase ... more Neighbour Joining tree of sequences of a standardised 648â bp region of the cytochrome c oxidase gene obtained from New Zealand and closely related bird species in this study. Bootstrap support values â Ľ0.5 are indicated. Monophyletic clades have been collapsed. Branches are coloured by Order. (PDF 6097 kb)
Cumulative error plot of type I (false positive) and type II (false negative) errors for differen... more Cumulative error plot of type I (false positive) and type II (false negative) errors for different divergence thresholds of maximum intraspecific and minimum interspecific genetic distances measured using a standardised 648â bp region of the cytochrome c oxidase gene for all New Zealand bird species with >â 1 specimen obtained during the study. The optimal threshold occurs at 0.25%. (DOCX 171 kb)
Despite 250 years of work in systematics, the majority of species remains to be identified. Risin... more Despite 250 years of work in systematics, the majority of species remains to be identified. Rising extinction rates and the need for increased biological monitoring lend urgency to this task. DNA sequencing, with key sequences serving as a "barcode", has therefore been proposed as a technology that might expedite species identification. In particular, the mitochondrial cytochrome c oxidase subunit 1 gene has been employed as a possible DNA marker for species and a number of studies in a variety of taxa have accordingly been carried out to examine its efficacy. In general, these studies demonstrate that DNA barcoding resolves most species, although some taxa have proved intractable. In some studies, barcoding provided a means of highlighting potential cryptic, synonymous or extinct species as well as matching adults with immature specimens. Higher taxa, however, have not been resolved as accurately as species. Nonetheless, DNA barcoding appears to offer a means of identifying species and may become a standard tool.
Pioglitazone is an antihyperglycaemic agent that, in the presence of insulin resistance, increase... more Pioglitazone is an antihyperglycaemic agent that, in the presence of insulin resistance, increases hepatic and peripheral insulin sensitivity, thereby inhibiting hepatic gluconeogenesis and increasing peripheral and splanchnic glucose uptake. Pioglitazone is generally well tolerated, weight gain and oedema are the most common emergent adverse events, and there are no known drug interactions between pioglitazone and other drugs. In clinical trials in patients with type 2 diabetes mellitus, pioglitazone as monotherapy, or in combination with metformin, repaglinide, insulin or a sulphonylurea, induced both long- and short-term improvements in glycaemic control and serum lipid profiles. Pioglitazone was also effective in reducing some measures of cardiovascular risk and arteriosclerosis. Pioglitazone thus offers an effective treatment option for the management of patients with type 2 diabetes.
Sources: medical literature published in any language since 1997 on adapalene, identified using M... more Sources: medical literature published in any language since 1997 on adapalene, identified using Medline and EMBASE, supplemented by AdisBase (a proprietary database of Adis International). Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug. Search strategy: Medline search terms were 'adapalene' or 'CD-271'. EMBASE search terms were 'adapalene' or 'CD 271'. AdisBase search terms were 'adapalene' or 'CD271'. Searches were last updated 10 May 2004. Selection: Studies in patients with acne vulgaris who received adapalene. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.
BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy, 2005
Anakinra (Kineret) is the first biologic drug that has been developed specifically as an interleu... more Anakinra (Kineret) is the first biologic drug that has been developed specifically as an interleukin (IL)-1 receptor antagonist (Ra) and is derived from an endogenous IL-1Ra. The drug blocks the activity of IL-1 in synovial joints, reducing the inflammatory and joint destructive processes associated with rheumatoid arthritis (RA). In randomized, placebo-controlled trials of up to 52 weeks' duration, anakinra has shown efficacy both as monotherapy and in combination with other disease-modifying antirheumatic drugs (DMARDs) in adults with RA. It is subcutaneously administered and is generally well tolerated. Anakinra offers a useful addition to the range of drugs available for the treatment of RA.
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