bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ketoconazole in the fathead minnow (Pimephales promelas): Reproductive toxicity and biological compensation
Authors: Ankley Gerald T. , Jensen Kathleen M. , Kahl Michael D. , Makynen Elizabeth A. , Blake Lindsey S. , Greene Katie J. , Johnson Rodney D. , Villeneuve Daniel L. 
Published: May 2007

AbstractKetoconazole (KTC) is a model pharmaceutical representing imidazole and triazole pesticides, which inhibit fungal growth through blocking a cytochrome P450 (CYP)-mediated step in ergosterol biosynthesis. Several of these fungicides have been shown to be reversible inhibitors of CYPs in vertebrates (primarily mammals), including CYP isoforms involved in the pathway that converts cholesterol to active sex steroids. In these studies, we assessed the effects of KTC on aspects of steroidogenesis and reproductive function in the fathead minnow (Pimephales promelas). Exposure of spawning adults to the fungicide for 21 d significantly decreased egg production at a water concentration as low as 25 μg/L. Despite evidence of reduced ex vivo testosterone production by gonads from KTC-exposed fathead minnows, circulating plasma concentrations of sex steroids (testosterone, 17β-estradiol) were not affected. Exposure to KTC caused an increase in the gonadosomatic index in both sexes and, in males, the fungicide caused a marked proliferation of interstitial (Leydig) cells. In addition, mRNA transcripts for two key steroidogenic enzymes, cytochrome P450 side-chain cleavage (CYP11A) and cytochrome P450 c17α hydroxylase/17,20 lyase (CYP17), were elevated by exposure to KTC. Both the changes in transcript levels and proliferation of gonad tissue represent potential adaptive or compensatory responses to impaired steroidogenic capacity. Overall our data indicate that, although KTC does adversely affect steroidogenesis and reproduction in the fathead minnow, the fish can compensate to some degree to mitigate effects of the fungicide. This has important implications for the interpretation of data from tests with endocrine-active chemicals.
Organochlorine pesticides in seafood products from Southern China and health risk assessment
Authors: Guo Jian-Yang , Zeng Eddy Y. , Wu Feng-Chang , Meng Xiang-Zhou , Mai Bi-Xian , Luo Xiao-Jun 
Published: May 2007

Abstract
Seafood consumption is an important route of human exposure to organic contaminants. Residual levels of organochlorine pesticides (OCPs), including DDTs, hexachlorocyclohexanes (HCHs), heptachlor, aldrin, α-endosulfan, β-endosulfan, dieldrin, endrin, endrin aldehyde, endrin ketone, methoxychlor, endosulfan sulfate, and heptachlor epoxide, were determined in a wide variety of seafood products collected from 11 coastal cities in southern China in June and October 2005. The results indicated that OCPs were predominated by DDTs and HCHs. The concentrations of other OCP components generally were low and were detectable in a small number of seafood samples only, probably reflective of the generally low levels of these OCPs in the study region and low bioaccumulation potentials in the species under investigation. Risk assessment against various standards clearly showed that seafood products were highly contaminated by DDTs and may pose health threat to local residents and the consumers all over the world. Furthermore, other OCP components, such as dieldrin and heptachlor, also impose lifetime cancer risk, especially to residents of coastal regions who often consume more seafood than those living inland. Therefore, continual monitoring of OCPs in various environment compartments, including biota and abiota, urgently is needed to mitigate effectively the impact of OCPs, particularly DDTs, on human health and the ecological environment.
Lethal and sublethal effects of chronic cadmium exposure on northern leopard frog (Rana pipiens) tadpoles
Authors: Gross Jackson A. , Chen Te-Hao , Karasov William H. 
Published: May 2007

Abstract
Data on the chronic effects of cadmium on amphibians are lacking in spite of widespread anthropogenic contamination of terrestrial and aquatic systems. We exposed embryos and tadpoles of northern leopard frogs (Rana pipiens) to Cd (control, 0.25, 5.0, and 20.0 μg/L as CdCl2, nominal concentrations) in a static renewal system from embryonic stages to complete tail resorption. Survival of embryos (Gosner stage [GS] 17–25) was greater than 97% in all treatments. Tadpole survival was negatively correlated with dose and was significantly reduced in the 5.0 and 20.0 μg/L treatments compared with controls. Tadpole survival was greater than 80% through GS 42, forelimb emergence, for all other treatments. Tadpoles exposed to 0.25 and 5.0 μg/L exhibited increased growth by week 11; tadpoles exposed to 5.0 μg/L were significantly younger at forelimb emergence. Whole-tadpole body burdens of Cd were positively correlated with increasing Cd treatments. Cadmium was shown to alter growth and development in a native amphibian species at ecologically relevant concentrations. The existing chronic water quality criterion for Cd appears to be protective of amphibians. However, additional studies with other chemicals are needed to further explore the potential for adverse effects of contaminants on the complex life cycle of amphibians.
Leaching and aging decrease nickel toxicity to soil microbial processes in soils freshly spiked with nickel chloride
Authors: Oorts Koen , Ghesquiere Uldeen , Smolders Erik 
Published: May 2007

AbstractNickel is a trace metal that exhibits pronounced long-term immobilization reactions in soil. It is unknown if the slowly decreasing solubility of Ni in soil on aging correlates with decreased toxicity to soil biota. Three uncontaminated soils (pH 4.5–7.6) were contaminated with NiCl2 and experimentally leached or incubated outdoors with free drainage for up to 15 months. Nickel toxicity was measured for three microbial processes (potential nitrification rate, glucose-induced respiration, and C mineralization of maize residue). Results for leached and aged samples were compared with results for these soils tested immediately after spiking. Experimental leaching increased Ni ED50s (Ni dose to inhibit process by 50%) with a median factor of 2.0, whereas Ni ED50s in soils aged 15 months were a factor 1 to 23 (median, 4.6) larger compared to freshly spiked soils. Changes in soil Ni toxicity on aging generally were largest in the soil with the highest pH, consistent with the largest relative decreases of soil solution Ni concentration or predicted Ni2+ activity. Soil solution Ni concentrations explained part, but not all, of the reduction in Ni toxicity. The predicted soil solution Ni2+ activity also did not fully explain the reduced toxicity, which was ascribed to the variable concentrations of ions competing with Ni2+ at biological membranes (e.g., H+, Mg2+, or Ca2+) among treatments. It is concluded that testing Ni toxicity to soil microbial processes immediately after spiking soils in the laboratory overestimates Ni toxicity compared to aged soils. Soil solution composition in freshly spiked soils clearly is different from that in leached or aged soils; therefore, soil spiked with metal salts should be leached before toxicity tests begin.
Tissue Doppler imaging for the detection and quantitation of myocardial dysfunction in patients with type 2 diabetes mellitus
Authors: Von Bibra Helene , Thrainsdottir Inga S , Hansen Alexander , Dounis Vasilios , Malmberg Klas , Rydén Lars 
Published: May 2007

The prevalence of type 2 diabetes mellitus is rapidly increasing. Myocardial dysfunction may be a consequence of diabetic cardiomyopathy and it contributes to the poor prognosis of diabetic patients. Aims This study was designed to test whether tissue Doppler imaging might be a suitable tool for early detection of myocardial dysfunction in diabetic patients. Methods Forty-three diabetic patients and 33 non-diabetic controls, including age-matched subgroups without evidence of coronary artery disease (n=12), were recruited if they had normal LV-function by standard 2-D echocardiography and no clinical signs of heart failure. They were investigated with tissue Doppler imaging at rest and during pharmacological stress with dipyridamole and/or dobutamine. Myocardial function was calculated as the mean value from six basal myocardial segments for peak velocity at systole (Vs), early diastole (Ve) and atrial contraction (Va). Results Compared to controls, diabetic patients had compromised Ve at rest (8.5. ± 1.7 vs. 9.6 ± 1.9 cm/sec, p<0.02), as did the subgroups without coronary artery disease (9.3 ± 1.7 vs. 10.7 ± 1.5 cm/sec, p<0.05). Dobutamine stress resulted in lower Vs (10.7 ± 2.7 vs. 13.6 ± 3.4 cm/sec, p<0.05) and Ve (10.0 ± 2.1 vs. 13.1 ± 3.8 cm/sec, p<0.05) in the diabetic patients, demonstrating an impaired increase of Vs, Vd and Va (p<0.05, p<0.0003 and p<0.03, respectively). An inverse correlation was observed between Ve and age in both control and diabetic individuals. Thus, abnormal values were defined in relation to age. Conclusions Diastolic and systolic myocardial dysfunction in patients with type 2 diabetes may be identified by quantitative tissue Doppler imaging before the onset of clinical signs of heart failure and before the appearance of traditional echocardiographic indices of systolic myocardial dysfunction.
Effect of rosiglitazone treatment on circulating vascular and inflammatory markers in insulin-resistant subjects
Authors: Chu James W , Abbasi Fahim , Lamendola Cynthia , McLaughlin Tracey , Reaven Gerald M , Tsao Philip S 
Published: May 2007

Thiazolidinedione (TZD) compounds enhance insulin sensitivity and attenuate inflammation. The effect of the TZD compound, rosiglitazone (RSG) on both actions was evaluated in two groups of insulin-resistant subjects with minimal elevations of fasting plasma glucose (PG) concentration: group A (n=15, PG < 7.0 mmol/L) and group B (n=14, PG 7.0–8.3 mmol/L). Insulin action, quantified by the insulin suppression test, improved after three months of treatment in both groups, and concentrations of C-reactive protein, plasminogen activator inhibitor-1 and E-selectin all fell. Significant decreases in L-selectin and P-selectin were confined to group B, and concentrations of interleukin-6, intercellular adhesion molecule-1 and vascular cellular adhesion molecule-1 did not fall in either group. Significant relationships were not discerned between enhanced insulin sensitivity and related variables and decreases in inflammatory/vascular markers, suggesting that RSG-induced changes in the latter variables in insulin-resistant individuals might be at least partly independent of the effects of the drug on insulin action.
Contrasting clinical and cardiovascular risk status between early and later onset type 2 diabetes
Authors: Hatunic Mensud , Burns Nicole , Finucane Francis , Mannion Cynthia , Nolan John J 
Published: May 2007

The prevalence of type 2 diabetes (T2DM) is increasing rapidly and the age of presentation is falling. These changes are likely to be linked to the current obesity epidemic. Our objective was to compare the characteristics of younger patients with T2DM (diagnosed at age < 40 years) with those of older patients (diagnosed at age 50–70 years). We identified 149 younger patients with T2DM, from our diabetes clinic database, and compared them with 217 older T2DM patients randomly identified from the same database. Younger patients with T2DM were more obese, more hypertriglyceridaemic, with lower high-density lipoprotein (HDL) cholesterol, higher total cholesterol/HDL ratio and worse initial and ongoing glycaemic control than older patients from the same clinic. Additional cardiovascular risk factors are associated with T2DM in the young. Treatment should be aimed at early modification of lifestyle and other forms of therapy to avoid long-term complications.
Platelet nitrate responsiveness in fasting and postprandial type 2 diabetes
Authors: Anderson Richard A , Ellis Gethin R , Evans L. Marc , Morris Keith , Chirkov Yuri Y , Horowitz John D , Jackson Simon K , Rees Alan , Lewis Malcolm J , Frenneaux Michael P 
Published: May 2007

Vascular responsiveness to exogenous nitrates in type 2 diabetes (T2DM) is attenuated in brachial and coronary vessels. We determined platelet responsiveness to nitric oxide (NO) in T2DM and control subjects. We examined whether the postprandial (PP) state affected platelet sensitivity to NO donors in T2DM patients and the extent of correlation between this and measures of oxidative stress, compared to changes in endothelial function. Twelve T2DM subjects were studied fasting and four hours after a test meal and compared with 15 healthy controls. We assessed the inhibitory effects of NO donors on adenosine 5′-diphosphate (ADP)-induced platelet aggregation. Oxidative stress was assessed by lipid-derived free radicals, ex vivo by electron paramagnetic resonance spectroscopy and markers of lipid peroxidation. Endothelial function was assessed by flow-mediated vasodilatation (FMD) of the brachial artery. Results are expressed as (mean±SEM). Fasting platelet aggregation was increased in diabetics versus controls (14.86±1.1 Ohms vs. 10.76±1.1 Ohms, p<0.05). Sodium nitroprusside (SNP) and glyceryl trinitrate (GTN) inhibited ADP-induced aggregation by 73.1±5.9% and 50.3±7.7% in healthy controls compared to 15.4±7% and 19.5±8.2% in T2DM (p<0.05). Fasting and postprandial inhibition of platelet aggregation with NO donors in T2DM was similar. T2DM patients had higher levels of oxidative stress in the fasting state and postprandially. There were no PP correlations with platelet NO resistance. In conclusion, there is platelet hyporesponsiveness to NO donors (SNP/GTN) in T2DM compared to controls, with increased ADP-induced platelet aggregation. Platelet abnormalities were associated with increased oxidative stress.
The importance of low serum levels of high-density lipoprotein cholesterol (HDL-C) as a cardiovascular risk factor
Authors: Espinosa-Larrañaga Francisco , Vejar-Jalaf Margarita , Medina-Santillán Roberto 
Published: May 2007

In order to discuss and establish a joint position on the treatment of low serum levels of high-density lipoprotein cholesterol (HDL-C), a group of experts involved in the care of people with dyslipidaemia and at risk of cardiovascular disease met in Miami, Florida, US, on 5th and 6th March 2005. The experts came from the Latin American countries Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Mexico and Venezuela and had at least five years of experience in the care of patients with dyslipidaemia and low HDL-C. The main objective of the meeting was to discuss and propose a treatment for low serum HDL-C levels as a cardiovascular risk factor in patients and to create a group of useful recommendations in this regard, applicable to the daily clinical practice of physicians dealing with patients with dyslipidaemia and cardiovascular disease. This document describes the methodology developed to obtain these recommendations and presents the results of this academic meeting.
The acute reperfusion management of STEMI in patients with impaired glucose tolerance and type 2 diabetes
Authors: Collet Jean-Philippe , Montalescot Gilles 
Published: May 2007

Diabetes mellitus (DM) remains an important predictor for mortality in patients with ST-segment Elevation Myocardial Infarction (STEMI) although the use of reperfusion therapy has resulted in a considerable improvement of survival. Of importance, newly diagnosed diabetic patients and those with fasting glycaemia in the diabetes range have even worse outcomes compared to patients with known diabetes. Overall, 50% of all patients presenting with STEMI have abnormal glucose metabolism of which fewer than 50% are known diabetics. Obviously, the efficacy of reperfusion therapy in reopening the occluded artery is similar in STEMI patients with or without impaired fasting glycaemia, while the pre-existing decreased myocardial perfusion in STEMI patients with impaired fasting glycaemia persists after successful epicardial revascularisation. There is no doubt that improving microvascular perfusion within the ischaemic myocardium remains the ultimate goal of managing STEMI patients with impaired glucose metabolism. Identification of defective myocardial perfusion together with an aggressive antithrombotic regimen, reduction of the inflammatory response of the ischaemic myocardium and improvement of glycaemia control represent promising therapeutic approaches that deserve additional specific clinical investigations. This review examines all these important issues.
New perspectives on the management of diabetic peripheral neuropathic pain
Authors: Jensen Troels S , Backonja Misha-Miroslav , Jiménez Sergio Hernández , Tesfaye Solomon , Valensi Paul , Ziegler Dan 
Published: May 2007

Peripheral neuropathy affects about 30% of people with diabetes mellitus. Between 16% and 26% of diabetes patients experience chronic pain. This may be referred to as diabetic neuropathic pain (DNP) or diabetic peripheral neuropathic pain (DPNP). Minimum requirements for diagnosis of DPNP should include assessment of pain and symptoms and neurological examination, with the accent on sensory examination. Given that depression and other co-morbidities are commonly associated with this condition, a broad approach to management is essential. Lifestyle intervention and optimisation of glycaemic control are recommended as initial steps in management. An evidence-based treatment algorithm for DPNP has been proposed, recommending initial use of either a tri-cyclic antidepressant, selective serotonin noradrenaline re-uptake inhibitor or alpha-2-delta agonist, depending on patient co-morbidities and contra-indications. Addition of an opioid agonist may be required in the event of inadequate pain control. Irrespective of which treatment is offered, only about one third of patients are likely to achieve more than 50% pain relief. Further research to improve the diagnosis and management of DPNP is needed.
Thiazolidinediones and risk for atherosclerosis: pleiotropic effects of PPARγ agonism
Authors: Patle Chetan B , De Lemos James A , Wyne Kathleen L , McGuire Darren K 
Published: May 2007

Despite advances in the development of anti-hyper-glycaemic drugs and a greater focus on cardiovascular risk modification for patients with diabetes, cardiovascular disease remains the most common complication of type 2 diabetes. Since their initial availability in 1997, the thiazolidinediones have become one of the most commonly prescribed classes of medications for type 2 diabetes. In addition to glucose control, the thiazolidinediones have a number of pleiotropic effects on myriad traditional and non-traditional risk factors for cardiovascular disease, and hold promise with regard to modification of cardiovascular risk. In a recently reported large-scale clinical trial, pioglitazone was associated with improved cardiovascular outcomes in patients with type 2 diabetes and prevalent atherosclerotic disease. In this review, we summarise the experimental, pre-clinical and clinical data regarding the effects of the thiazolidinediones on cardiovascular risk factors and clinical outcomes.
Postprandial hyperglycaemia and vascular damage - the benefits of acarbose
Authors: Båvenholm Peter N , Efendic Suad 
Published: May 2007

Traditional risk factors do not fully explain the increased risk of cardiovascular disease (CVD) in diabetes. Epidemiology shows that hyperglycaemia is a continuous CVD risk factor and that two-hour postprandial glucose levels are more strongly associated with CVD than fasting glucose. Good glycaemic control is proven to reduce the risk of microvascular complications, but equivalent evidence for CVD risk reduction is lacking. However, in the Study to Prevent Non-Insulin Dependent Diabetes Mellitus (STOP-NIDDM), acarbose reduced the risk of diabetes in those with impaired glucose tolerance by 36% (p=0.0017) and the risk of any cardiovascular event by 49% (p=0.0326) versus placebo. Furthermore, a meta-analysis of trials of acarbose in patients with type 2 diabetes suggests a significant reduction of CVD events. This review examines evidence that postprandial hyperglycaemia plays a major role in vascular damage, particularly through non-traditional risk factors such as oxidative stress and subclinical inflammation, and how acarbose may prevent this damage.
The sibutramine metabolite M2 improves muscle glucose uptake and reduces hepatic glucose output: preliminary data
Authors: Coletta Dawn K , Bates Sarah H , Jones Robert B , Bailey Clifford J 
Published: May 2007

The satiety agent sibutramine acts in part through a primary amine metabolite, M2. To investigate whether M2 could affect glycaemia independently of satiety and weight loss, groups of normal mice received a single dose of M2 (1 or 10 mg/kg) and food was withheld. Compared with controls (who received vehicle only), M2 (10 mg/kg) decreased basal plasma glucose concentrations, with a maximal decrease of about 25% at 4-8 hours (p<0.05). Soleus muscles were isolated from the mice at intervals: insulin-mediated glucose uptake by the muscles from controls progressively decreased over 24 hours whereas uptake was maintained by muscles from M2-treat-ed mice. Hepatic gluconeogenesis was reduced about 40% by liver snips isolated from M2-treated mice after 24 hours (p<0.05). These preliminary results suggest that the M2 metabolite of sibutramine can reduce glycaemia, maintain insulin-mediated muscle glucose uptake and reduce hepatic gluconeogenesis independently of satiety and weight loss.
Treating insulin resistance: future prospects
Authors: Bailey Clifford J 
Published: May 2007

Insulin resistance typically reflects multiple defects of insulin receptor and post-receptor signalling that impair a diverse range of metabolic and vascular actions. Many potential intervention targets and compounds with therapeutic activity have been described. Proof of principle for a non-peptide insulin mimetic has been demonstrated by specific activation of the intracellular B-subunit of the insulin receptor. Potentiation of insulin action has been achieved with agents that enhance phosphorylation and prolong the tyrosine kinase activity of the insulin receptor and its protein substrates after activation by insulin. These include inhibitors of phosphatases and serine kinases that normally prevent or terminate tyrosine kinase signalling. Additional approaches involve increasing the activity of phos-phatidylinositol 3-kinase and other downstream components of the insulin signalling pathways. Experimental interventions to remove signalling defects caused by cytokines, certain adipocyte hormones, excess fatty acids, glucotoxicity and negative feedback by distal signalling steps have also indicated therapeutic possibilities. Several hormones, metabolic enzymes, minerals, co-factors and transcription co-activators have shown insulin-sensitising potential. Since insulin resistance affects many metabolic and cardiovascular diseases, it provides an opportunity for simultaneous therapeutic attack on a broad front.