bluuebunny/crossref_metadata_2025 huggingface dataset:
Structures and Magnetic Properties of Di- and Trinuclear Nickel(II) Complexes with Phenoxo and Acetato Bridges
Authors: Koizumi Satoshi , Nihei Masayuki , Oshio Hiroki
Published: August 2003

Reactions of NiCl2·6H2O and Ni(CH3COO)2·4H2O with tridentate ligand yielded di- and trinuclear nickel(II) complexes of [Ni2(HL1)2Cl2(MeOH)2] (1) and [Ni3(HL2)2(CH3COO)4(MeOH)2] (2) (H2L1 = N-(2-hydroxybenzyl)ethanolamine), H2L2 = N-(2-hydroxybenzyl)propanolamine), respectively; the magnetic susceptibility measurements revealed that 1 and 2 have singlet and septet spin ground states, respectively.
Friedel–Crafts Benzylation and Phenethylation Reactions Using Benzyl and Phenethyl Benzothiazol-2-yl Carbonate Derivatives
Authors: Mukaiyama Teruaki , Kamiyama Hiroaki , Yamanaka Hiroyuki
Published: August 2003

Friedel–Crafts benzylation and phenethylation reactions of several aromatic compounds with benzyl and phenethyl benzothiazol-2-yl carbonate derivatives were carried out in the presence of scandium triflate (Sc(OTf)3) as a catalyst. Suitable combinations of the leaving group of carbonates and acid promoters that generate cationic alkyl species were examined.
Direct Production of Hydrogen Peroxide from H2 and O2 over Highly Dispersed Au catalysts
Authors: Okumura Mitsutaka , Kitagawa Yasutaka , Yamagcuhi Kizashi , Akita Tomoki , Tsubota Susumu , Haruta Masatake
Published: August 2003

Highly dispersed Au catalysts were active for the direct formation of H2O2 form H2 and O2. Especially, the rate of H2O2 production greatly increased when Au nanoparticles were deposited onto SiO2, MCM-41 and active carbon supports.
Condensation of α-Amino Acid with Amine in the Absence of a Coupling Agent
Authors: Yamaguchi Jun-ichi , Nagai Shinya , Fukuoka Emi , Suyama Takayuki
Published: August 2003

Treatment of N-(4-nitrophenoxycarbonyl)amino acid with an equimolar amount of amine in the absence of a coupling agent gave the corresponding α-amino acid amide in high yield.
Well-aligned ZnO Whiskers Prepared by Catalyst-assisted Flux Method
Authors: Kong Xianghua , Li Yadong
Published: August 2003

Well-aligned ZnO whiskers were prepared by a catalyst-assisted flux method using ZnS powders as starting materials at a temperature of 860 °C. Au coating on the Si substrate plays a key role on the nucleation. The growth of ZnO whiskers was controlled by a high temperature SLS mechanism.
Photochromism of Aza-aromatics with Hydroxy Group. Intermolecular Proton Transfer in Glassy Solution
Authors: Ogawa Keiichiro , Miura Masatoshi , Nakayama Toshio , Harada Jun
Published: August 2003

When solutions of 2-hydroxyphenazine (1), 3-hydroxyacridine (2), and 7-hydroxyquinoline (3) were irradiated with UV light at 77 K, they became deeply colored. The color of the solutions reverted to the original one, when they were left in the dark at 77 K or at a higher temperature. We ascribe the photochromism to proton tautomerization, which is most likely induced by an intermolecular proton transfer in the excited state.
57Fe Mössbauer Study on Photoinduced Spin Transition of Ferrocene in Polymer Matrices
Authors: Einaga Yasuaki , Kotake Masahiro , Yamada Yasuhiro , Sato Osamu
Published: August 2003

A polymer matrix isolation technique was examined as a potentially novel strategy for realizing optically switchable materials. Not only was a ferricinium ion ([Cp2FeIII]+) produced, but also was produced an isomer of ferrocene (Cp2Fe) with high spin FeII in a poly(methyl methacrylate) (PMMA) matrix film containing CCl4 by the photoillumination of ferrocene at low temperature. The high spin state could be maintained for an extended period when the sample was kept below ≈130 K. This is the first observation of a photoinduced spin transition for ferrocene. The strategy that we used to achieve the spin transition using optical stimuli may open up many possibilities for the development of new magneto-optical devices.
Morphology of the Pancreas in Normal and Diabetic States
Authors: Clark A.
Published: August 2003

The islets of Langerhans form 5% of the pancreatic mass and are distributed throughout the pancreatic exocrine tissue. Islets are composed of cells containing insulin (β‐cells), glucagon (α‐cells), somatostatin (δ‐cells), and pancreatic polypeptide (PP‐cells) and have secretory granules with different characteristic morphologies. In type 1 diabetes, autoimmune destruction of β‐cells is associated with insulitis in the acute phase of the disease; other islet cells remain unaffected in islets of reduced size. Islets in type 2 diabetic subjects are not reduced in size and there is no evidence for a reduction in islet numbers or changes in the proportion of endocrine cells in most affected patients. Islet amyloid deposits formed from islet amyloid polypeptide are found in a proportion of islets (0.1–90% of islets) in more than 90% of patients at postmortem but these deposits are not a causal factor for type 2 diabetes in humans. Severe islet amyloid deposition is related to a reduction of islet cell mass and requirement for insulin therapy. Reduced islet cell mass is associated with genetically determined diabetes involving genes regulating metabolism and transcription factors (e.g. MODY, mitchondrial diabetes, Wolfram syndrome). Exocrine diseases such as pancreatitis, cystic fibrosis, and calcific pancreatitis lead to diabetes, indicating the functional association of the exocrine and endocrine pancreas.
Insulin Gene Expression and Biosynthesis
Authors: Poitout Vincent , Stein Roland , Rhodes Christopher J.
Published: August 2003

The insulin gene is expressed specifically and at very high levels in pancreatic β‐cells. Most of its tissue‐specific expression and metabolic regulation are conferred by approximately 340 bp upstream of the transcription initiation site. Several glucose‐responsive elements have been identified within this region, and physiological regulation of insulin gene expression relies on the cooperative and synergistic interactions between DNA‐binding factors and coactivators. Glucose is the major regulator of insulin gene expression. It activates transcription and stabilizes insulin mRNA. In addition, insulin gene expression is stimulated by glucagon‐like peptide 1, growth hormone, and lactogenic hormones, and inhibited by epinephrine, somatostatin, glucagon, and leptin. In type 2 diabetes, chronic elevations of blood glucose and fatty acid levels impair insulin gene expression. Under most circumstances, the production of insulin is also highly regulated at the translational level. Indeed, this is the predominant control mechanism in the β‐cell whereby intracellular insulin stores are efficiently maintained in the short term. Essentially, translation of the preproinsulin mRNA template to preproinsulin protein occurs in a fashion typical of most eukaryotic mRNAs. In general, nutrients that stimulate insulin secretion, of which glucose is the most physiologically relevant, also stimulate proinsulin biosynthesis at the translational level. Recently, it has been shown that specific control of glucose‐induced proinsulin biosynthesis in the β‐cell resides incis‐elements in the 5′‐ and 3′‐untranslated regions of preproinsulin mRNA itself. After proinsulin is translocated into the lumen of the rough endoplasmic reticulum, correctly folded proinsulin can then be delivered in transport vesicles to thecis‐Golgi apparatus in an ATP‐dependent process. The major site for processing of the proinsulin to biologically active insulin is the immature granule compartment of the β‐cell. Production of insulin occurs via limited proteolysis of the proinsulin precursor molecule, which is catalyzed by two endopeptidases, proprotein convertase 2 (PC2) and proprotein convertase 3 (PC3) (also known as PC‐1), and an exopeptidase, carboxypeptidase‐H (CP‐H). Similar to their deleterious effects on insulin gene expression, chronic hyperglycemia and hyperlipidiemia impair proinsulin biosynthesis.
β‐Cell Biology of Insulin Secretion
Authors: Wollheim Claes B. , Maechler Pierre
Published: August 2003

Blood glucose homeostasis critically depends on the precise regulation of insulin secretion from the pancreatic β‐cells. The chapter describes how glucose enters the β‐cell, is phosphorylated, and yields metabolic coupling factors mainly in the mitochondria. These factors modify K+and Ca2+fluxes across the plasma membrane. It is discussed how cytosolic Ca2+triggers exocytosis of the insulin stored in the secretory granules. This process is under tight control of proteins implicated in granule movement, docking, and ultimate fusion with the plasma membrane, resulting in insulin release. Certain β‐cell defects are also illustrated, in particular those linked to mitochondrial dysfunction or mutations in key proteins involved in metabolism–secretion coupling.
Normal Insulin Secretion in Humans
Authors: Utzschneider Kristina M. , Porte Daniel , Kahn Steven E.
Published: August 2003

Normal insulin secretion in humans is mainly regulated by glucose, but additional factors including other nutrients, hormones, and neural input play an important role. In the basal state, insulin is released in a rapid pulsatile manner, with pulses occurring every 6–10 min. These pulses are superimposed on an oscillatory pattern of 11–15 oscillations per 24 h. Dynamic insulin release also occurs in response to stimuli. The insulin response to intravenous glucose has been shown to have two distinct phases: an early first phase response lasting for 10 min, and a slower longer second phase response lasting as long as the glucose level is elevated. Preexistent elevations in the plasma glucose level are able to increase the insulin response to a subsequent glucose stimulus, an effect called priming. Glucose is also capable of potentiating the insulin response to non‐glucose secretagogues such as amino acids, peptides, and sulfonylureas. Non‐glucose factors that affect insulin secretion include amino acids, free fatty acids, medications, and the response to stress. Neural inputs regulate islet secretory function through both the sympathetic and parasympathetic nervous systems. The gastrointestinal peptides glucagon‐like peptide 1 (GLP‐1) and glucose‐dependent insulinotropic polypeptide (GIP), released from the intestine during oral intake, have been found to play a significant role in augmenting insulin release, an effect known as the incretin effect. When assessing the effect of all these different secretagogues on β‐cell function, it is important to take into account the prevailing insulin sensitivity, as variations in insulin sensitivity lead to compensatory changes in insulin release. Understanding the dynamics and complex regulation of normal insulin secretion in humans provides the basis for understanding the consequences of β‐cell dysfunction observed in diabetes.
Neuropeptides and Insulin Secretion
Authors: Ahrén Bo
Published: August 2003

The pancreatic islets are richly innervated by parasympathetic, sympathetic, and, sensory nerves and these nerves have been shown to be of importance for the regulation of islet function. The terminals of the islet autonomic nerves harbor, however, not only the classical neurotransmitters, acetylcholine and noradrenaline, but also several neuropeptides. These neuropeptides are vasoactive intestinal polypeptide (VIP), pituitary adenlyate cyclase activating polypeptide (PACAP), and gastrin releasing peptide (GRP) in the parasympathetic nerve terminals; galanin and neuropeptide Y (NPY) in the sympathetic nerve terminals; and calcitonin gene‐related peptide (CGRP) and substance P (SP) in the sensory nerves. These neuropeptides may mediate activation of the autonomic nerves on islet hormone secretion. Thus, insulin secretion stimulated by parasympathetic nerves may be mediated by VIP, PACAP, and GRP, which all stimulate insulin secretion, whereas inhibition of insulin secretion by sympathetic nerve activation may be mediated by galanin and NPY, which both inhibit insulin secretion. The neuropeptides in the sensory nerve terminals—CGRP and SP—inhibit insulin secretion.

The actions of the neurotransmitters on insulin secretion are elicited by different receptors affecting different signaling pathways in the β‐cells. For example, VIP and PACAP activate adenylate cyclase and GRP activates phospholipase C, whereas galanin and NPY inhibit adenylate cyclase. In addition, the neurotransmitters affect ionic channel activity and exert direct influences on the exocytosis machinery.

The islet autonomic nerves seem to be of physiological importance for insulin secretion in various conditions. Thus, parasympathetic nerves mediate the cephalic phase of insulin secretion after a meal intake and synchronize the islets to function as a unit, allowing oscillations of islet hormone secretion. The sympathetic nerves optimize islet hormone secretion during metabolic stress or physical activity. The autonomic nerves might also be involved in the islet adaptation to insulin resistance with possible implication for the development of glucose intolerance and type 2 diabetes.

The islet innervation is thus of importance both for the physiology and pathophysiology of the islets through contribution by all branches of the autonomic nerves and several different neurotransmitters.
Biological Effects of C‐peptide and Proinsulin
Authors: Wahren John , Ekberg Karin , Shafqat Jawed , Johansson Jan , Johansson Bo‐Lennart , Jörnvall Hans
Published: August 2003

C‐peptide: In contrast to the earlier view, new data now indicate that proinsulin C‐peptide does exert important physiological effects and shows the characteristics of an endogenous peptide hormone. C‐peptide in nanomolar concentrations binds specifically to cell membranes, probably to a G‐protein coupled receptor, resulting in subsequent activation of Ca2+‐ and MAP‐kinase‐dependent signaling pathways. C‐peptide's binding to cell membranes is stereospecific and the C‐terminal pentapeptide segment participates in the process. Some studies indicate that C‐peptide and insulin may exert a synergistic effect on the insulin signaling pathway. C‐peptide stimulates Na+,K+‐ATPase and endothelial nitric oxide synthase activities. C‐peptide administration in replacement doses in animal models of diabetes or in type 1 diabetic patients results in increased blood flow in skeletal muscle, myocardium, kidney, nerve, and skin. C‐peptide replacement decreases glomerular hyperfiltration, reduces urinary albumin excretion, and corrects glomerular expansion. It also increases nerve conduction velocity, improves sensory nerve function, and reduces or reverses the characteristic diabetes‐induced nodal and paranodal nerve structural changes. The evidence suggests that replacement of C‐peptide together with insulin may be beneficial in patients with type 1 diabetes and serve to retard or prevent the development of long‐term complications.Proinsulin: Only a very small proportion of proinsulin is released in its intact form to the circulation in healthy subjects. In contrast, in type 2 diabetes, plasma proinsulin and its conversion intermediates may be higher than in healthy individuals. Proinsulin binds to the insulin receptor with approximately 10% of insulin's affinity. The suggestion of a specific effect of proinsulin in lowering hepatic glucose output has not been verified in direct studies. Clinical trials designed to evaluate the usefulness of proinsulin as an insulin analogue in type 2 diabetic patients were discontinued because of increased incidence of myocardial infarction. Recent reports of specific high affinity proinsulin receptors in several tissues are intriguing and warrant further investigation.
Biosynthesis, Secretion, and Action of Glucagon
Authors: Lefèbvre Pierre J.
Published: August 2003

Glucagon is a very ancient and tightly conserved molecule and is an important hormone exerting numerous metabolic effects, including stimulation of hepatic glycogenolysis, gluconeogenesis, and ketogenesis; inhibition of liver glycogen synthesis; and, at least in some species, stimulation of adipose tissue lipolysis. All these effects of glucagon are strongly antagonized by insulin. Glucagon originates in the A‐cells of the islets of Langerhans of the pancreas, where it is synthesized in the form of a large precursor, preproglucagon. Several peptides derived from the preproglucagon molecule are also expressed in the gut and the brain; they include glicentin, oxyntomodulin, glucagon, and glucagon‐like peptides 1 and 2, while a smaller molecule, mini‐glucagon, is generated at the hormone target cells. Glucagon release is increased in various physiological situations including hypoglycemia, low circulating levels of free fatty acids, high levels of numerous amino acids, and stimulation of both vagal and adrenergic nervous systems. Prolonged starvation, long‐lasting exercise, stress, and adaptation to the extrauterine life are also associated with high circulating levels of glucagon. All these effects of glucagon make it above all a “hormone of energy need.” Diabetes is characterized by excessive circulating levels of glucagon, which are now considered to stem largely from the absolute or relative insulin deficiency that is observed in this syndrome. Studies are in progress to identify inhibitors or glucagon secretion or action as new tools in the pharmacological treatment of diabetes.
Islet Amyloid Polypeptide/GLP‐1/Exendin
Authors: Baggio Laurie L. , Drucker Daniel J.
Published: August 2003

Gastrointestinal peptides exert important physiological roles in the control of feeding behavior, gut motility, nutrient absorption, and energy assimilation. Islet amyloid polypeptide is secreted from islet β‐cells, and exerts inhibitory actions on appetite, gastric motility, and glucagon secretion. Glucagon‐like peptide 1 (GLP‐1) is released from enteroendocrine cells and regulates food intake, gastric emptying, insulin and glucagon secretion, and β‐cell proliferation and apoptosis. Exendin‐4, a lizard‐derived peptide, is a potent and stable GLP‐1R agonist that exerts GLP‐1‐like actionsin vivo. The overlapping glucose‐lowering properties of these peptides have fostered considerable interest in their development as new therapeutic agents for the treatment of diabetes mellitus.
The Genetics of Human Obesity
Authors: Bouchard Claude , Pérusse Louis
Published: August 2003

This chapter summarizes the research on the role of genetic variation in human obesity. It provides a brief review of our current understanding of the level of heritability and of the familial risk for increasing levels of excess body weight. Single‐gene defects known to cause obesity are discussed. The results of a large number of association studies performed with candidate genes are described. The candidate genes with at least five positive studies are highlighted. All published genomic scan studies relevant to obesity are reviewed, with an emphasis on the linkage results characterized by apparent convergence in at least two cohorts. Finally, the role of gene–environment interactions in the response to chronic positive or negative energy balance is examined.
Role of the Adipocyte in Type 2 Diabetes
Authors: Farmer Stephen R. , Prusty Deepanwita
Published: August 2003

Obesity is a major risk factor for several pathophysiological disorders including type 2 diabetes and cardiovascular disease. Obese individuals, particularly those with excess adipose tissue around their major organs, lose the ability to respond to insulin and eventually develop hyperinsulinemia and hyperlipidemia. If left untreated, these individuals are at risk for developing type 2 diabetes and cardiovascular disease. Investigations during the last few years have focused on the adipocyte as a potential link between obesity and insulin resistance. The conclusions drawn from this research implicate the adipocyte as a central player in the development of insulin resistance, affecting muscle and liver of individuals with excess adipose tissue. In fact, the role of the adipocyte in regulating overall energy balance has been significantly redefined. Specifically, in addition to storing excess energy as triglycerides, adipocytes secrete many biologically active molecules that regulate mechanisms related to energy balance in other metabolically active tissues including the brain, muscle, and liver. These bioactive molecules include hormones and several cytokines, collectively referred to as
adipocytokines
, which include leptin, tumor necrosis factor α (TNF‐α), adiponectin/ACRP30/adipoQ/apM1, and resistin. Certain adipocytokines have been directly linked to insulin resistance in obese humans as well as in various animal models. An approach to combating type 2 diabetes mellitus, therefore, is to understand the molecular and physiological mechanisms that regulate the formation and function of adipocytes in specific adipose tissue depots. This chapter discusses the role of adipogenic transcription factors in regulating adipogenesis and metabolic homeostasis. Attention is given to the nuclear hormone receptor PPAR‐γ (peroxisome proliferator‐activated receptor γ) which is a master regulator of adipocyte differentiation and the target of the thiazolidinedione family of antidiabetic drugs. In this regard, the mechanism of action of the thiazolidinediones is discussed and other adipocyte proteins are proposed as alternative targets for the development of antidiabetic therapeutics.
Animal Models of Obesity
Authors: York David A.
Published: August 2003

Animal models have played an important role in advancing our understanding of the causes and consequences of obesity. The spontaneous single gene mutations led to the discovery of leptin and the melanocortin signaling pathways and were important to the understanding of hypothalamic systems that control energy balance. The use of transgenic and gene targeting technologies has opened a new era of investigation, identifying new genes that regulate the development or prevention of obesity and providing the tools for proof of function of genes. These studies have shown that a wide range of genes expressed primarily in the central nervous system or in adipose tissue are potential targets for the treatment of obesity.
Is Type 2 Diabetes the Result of a “Thrifty Genotype” or a “Thrifty Phenotype”?
Authors: Lindsay Robert S.
Published: August 2003

While a number of important risk factors for development of type 2 diabetes have been described—most notably overweight and obesity—much of the detail of the etiology of the disease remains unknown. Both genetic and environmental factors will be important and disease risk is likely to reflect a complex interaction of both. Certain aspects of the epidemiology of type 2 diabetes, the widespread predisposition to the disease, increased predisposition in certain ethnic groups, and more recently, well‐described associations of diabetes risk and lower birth weight have prompted a number of hypotheses. These hypotheses attempt to explain these important epidemiological features of type 2 diabetes but also place our understanding of the etiology of type 2 diabetes in a wider context. A unifying theme of the thrifty genotype and thrifty phenotype hypotheses is the concept that predisposition to type 2 diabetes may reflect previous nutritional conditions. In the case of the thrifty genotype the nutritional history of populations favors genetic polymorphisms, which also render individuals diabetes prone. By contrast the thrifty phenotype proposes that adverse nutritional conditions in the early environment predispose to later disease in individuals. Both hypotheses are connected by a further underlying aim—to aid our understanding of the causes of type 2 diabetes and thus find ways to prevent, treat, and ultimately cure the disease.
Treatment of Obesity
Authors: Astrup Arne
Published: August 2003

Obesity is the major environmental factor in the development of type 2 diabetes in high‐risk subjects and even a minor weight loss can prevent the disease. Randomized trials using diet, weight loss agents, or surgical treatment of obesity have all clearly demonstrated that body fat loss is crucial in improving insulin resistance and reducing the risk of diabetes, whereas diet composition and physical activity play minor roles. Weight loss improves glycemic control in type 2 diabetic patients and has a clinically relevant beneficial effect on all cardiovascular risk factors. Weight management programs are a cornerstone in both the prevention and treatment of type 2 diabetes. A professional team (physician and dieticians or nurses) specializing in weight loss and maintenance can help almost all simple and diabetic obese patients achieve a weight loss of 5–10%. Higher daily physical activity levels and regular exercise increase daily energy expenditure and enhance insulin sensitivity in weight maintenance, but have no significant effect on rate of weight loss. Weight loss drugs have a role in the treatment of patients in whom lifestyle modification fails to produce the required weight control. Bariatric surgery is a very effective means to produce a longer lasting weight loss, and may be an option in severely obese patients who are difficult to treat with the other weight management tools.
Lipodystrophies and Diabetes
Authors: Garg Abhimanyu , Misra Anoop
Published: August 2003

Lipodystrophies are heterogeneous disorders of adipose tissue, characterized by selective loss of body fat and a predisposition to develop insulin resistance, diabetes mellitus, hyperlipidemia, and hepatic steatosis. These disorders can be either genetic or acquired. The extent of fat loss can also vary from being localized or partial to generalized. Among the genetic lipodystrophies, congenital generalized lipodystrophy is caused by mutations in 1‐acylglycerol‐3‐phosphateO‐acyltransferase 2 (AGPAT2) and Berardinelli–Seip Congenital Lipodystrophy 2 (BSCL2) genes and familial partial lipodystrophies by defects in lamin A/C (LMNA) and peroxisome proliferator‐activated receptor γ (PPARG) genes. Acquired generalized and partial lipodystrophies are likely to be autoimmune diseases. Lipodystrophy in HIV‐infected patients is mainly due to prolonged treatment with HIV‐1 protease inhibitors. Diabetes in patients with lipodystrophies may be caused by severe insulin resistance (hepatic and peripheral) and decrease in the insulin secretion due to pancreatic islet amyloidosis and β‐cell atrophy. Hyperglycemia is difficult to manage despite large doses of insulin but does not lead to ketosis. Recombinant human leptin has been reported to drastically improve hyperglycemia and hypertriglyceridemia in lipodystrophy patients with low serum leptin levels. It is hoped that our understanding of the pathogenesis of these disorders will contribute to a better understanding of adipocyte physiology, and of the molecular mechanisms of insulin resistance and eventually to better therapeutic options.
Clinical Features and Treatment of Coronary Heart Disease in Diabetes
Authors: Gray Rosaire P. , Yudkin John S.
Published: August 2003

Morbidity and mortality from cardiovascular disease are two to five times higher in patients with diabetes mellitus compared with nondiabetic patients. The atherosclerotic lesion in diabetes mellitus is histologically similar to that in nondiabetic populations but is more extensive and severe. There is clustering of the major risk factors for cardiovascular disease, smoking, hypertension, and hyperlipidemia in diabetic subjects but the excess risk of coronary heart disease (CHD) remains after adjusting for levels of all other known risk factors, suggesting that diabetes is an independent risk factor for cardiovascular disease. The clinical manifestations of CHD are similar to that in nondiabetic subjects; however, silent ischemia and myocardial infarction are more common. The principles of management of angina, acute coronary syndromes, myocardial infarction, and heart failure are similar to that in the nondiabetic population. Until recently, most of the large randomized trials that have evaluated primary and secondary prevention therapies have not randomized large numbers of diabetic subjects and therefore much of the evidence is based on subgroup analysis and extrapolation from nondiabetic populations. A number of publications exist to guide primary and secondary prevention of CHD in the general population and these are summarized with particular reference to the diabetic patient, with emphasis on aggressive reduction of risk factors. Indications for coronary angiography in diabetic patients with symptomatic coronary disease are similar to those in nondiabetic patients, recognizing the increased risk associated with revascularization procedures in diabetes mellitus. There is an increased risk of mortality following both coronary bypass surgery and angioplasty, and there is a substantially increased risk of restenosis following angioplasty in diabetic patients, probably partly ameliorated by the use of coronary stents. Much of this increased risk is due to confounding associations, e.g. female sex, diffuse coronary disease, impaired left ventricular function, and renal impairment, rather than the diabetic state itself.
Peripheral Vascular Disease in Diabetes
Authors: Schaper Nicolaas C. , Kitslaar Peter J.E.M
Published: August 2003

Peripheral arterial disease is a common finding in patients with diabetes mellitus. In many patients the disease has no or few symptoms and runs a relatively benign course. However, in others it leads to gangrene or impaired healing of a neuro‐ischemic foot ulcer, with amputation as a final result. Moreover, peripheral arterial disease (PAD) can be seen as a sign of severe generalized atherosclerosis, which should be treated aggressively. Peripheral arterial disease of the lower extremities, here abbreviated as PAD, is defined as signs, symptoms, or abnormal noninvasive tests in one or both legs attributable to obstructive atherosclerotic disease. Critical limb ischemia was recently defined as chronic ischemic rest pain, ulceration, or gangrene attributable to objectively proven arterial occlusive disease. The term critical limb ischemia implies chronicity. In contrast, acute limb ischemia is a sudden event, usually due to an embolus or thrombosis in preexistent PAD. In this chapter we discuss basic and clinical aspects of PAD in diabetic patients, with the patient in a diabetic clinic as a starting point. In the treatment of these patients a close cooperation between diabetologist and vascular surgeon is needed. Therefore, background information is given on several surgical procedures.
Hemostatic Abnormalities in Diabetes
Authors: Juhan‐Vague Irène , Emmanuel Morange Pierre , Alessi Marie‐Christine
Published: August 2003

Insulin‐ and non‐insulin‐dependent diabetes and obesity with insulin resistance are accompanied by a prothrombotic state that favors thrombosis at the site of a suddenly ruptured atherosclerotic plaque and is also involved in the progression of atherosclerosis itself. This dysregulation of hemostasis includes activation of endothelial cells, leukocytes, and platelets, hypercoagulability with increased formation of the multipotent thrombin, and decreased fibrinolytic activity due to increased plasma levels of plasminogen activator inhibitor 1 (PAI‐1). The long‐lasting influence of these disorders exerts a progressive deleterious influence on the atherothrombotic process.

The mechanisms that induce this prothrombotic state are multifactorial:

Hyperglycemia leads to glycation of membrane and circulating proteins, inducing consequent functional changes and inflammation.

Low‐grade inflammation with prolonged cytokine‐mediated acute phase reaction leads to cell activation and increased synthesis of hemostatic parameters such as fibrinogen, the main substrate of thrombin, von Willebrand Factor, and factor VIII.

Insulin resistance also involves proinflammatory cytokines such as the tumor necrosis factor pathway, which could be the cause of the observed dramatic decrease in fibrinolysis due to increased expression of PAI‐1. Studies conducted in mice or epidemiological studies have shown recently that increased plasma PAI‐1 levels and increased PAI‐1 expression in tissues could influence adipose tissue growth and the development of atherosclerosis as well as that of type 2 diabetes. Thus, PAI‐1 could represent a target for therapeutic intervention.
Cerebrovascular Disease in Diabetes Mellitus
Authors: Gray Christopher S.
Published: August 2003

Diabetes mellitus is an important risk factor for ischemic stroke. For many diabetic patients stroke is a recurrent disorder leading to cumulative disability, cognitive impairment, and reduced quality of life. Diabetic patients are also at increased risk of vascular dementia through processes that extend beyond clinically manifest and silent stroke and overlap with the pathophysiological changes of Alzheimer's type pathology. There is as yet no evidence that intensive control of diabetes can prevent vascular dementia. The extent to which diabetes is a risk factor for stroke is often underrecognized and many patients may not receive optimal secondary preventive treatment. Strategies to reduce the risk of first ever and recurrent stroke in diabetic subjects have now been clarified in large randomized controlled trials. Intensive management of hypertension and dyslipidemia has been shown to independently reduce the risk of cerebrovascular disease. For patients who have had a stroke, hyperglycemia with or without a previous history of diabetes is a frequent finding and is associated with a poor prognosis. Hyperglycemia may also adversely influence the safety and efficacy of other stroke treatments. The benefit of routine treatment to reverse this association is not as yet proven.
Metabolic Stress and Atherosclerosis
Authors: Reusch Jane E.-B. , Brownlee Michael
Published: August 2003

Diabetes is associated with accelerated atherosclerotic macrovascular disease affecting arteries that supply the heart, brain, and lower extremities. As a consequence, patients with diabetes have a much higher risk of myocardial infarction, stroke, and limb amputation. The excess risk associated with diabetes remains even after adjustment for traditional coronary heart disease risk factors such as smoking, hypertension, and hypercholesterolemia. Type 2 diabetic patients without a previous myocardial infarction have as high a risk of myocardial infarction over 7 years as nondiabetic patients with a previous myocardial infarction. Type 1 diabetes results in nearly 100% atherosclerosis by the fifth decade of life. The mechanisms by which diabetes confers this increased risk are much less clear than those responsible for diabetic microvascular disease, but associational studies suggest that the metabolic derangements caused by insulin resistance and insulin deficiency are involved. These include dyslipoproteinemia, excess free fatty acid flux, and hyperglycemia. In this chapter we review recent findings on the mechanisms whereby high glucose and high FFAs, present in both type 1 and type 2 diabetes, lead to vascular dysfunction and injury. Pathways involving advanced glycation end products, protein kinase C, NF‐κB, aldose reductase, hexosamine, and CREB (cAMP response element binding protein) are reviewed. Both hyperglycemia and high free fatty acid flux lead to increased vascular oxidative stress, which appears to activate all of these signaling pathways, leading to diabetic macrovascular disease.
Organization of Care: Problems in Developing Countries—Sub‐Saharan Africa
Authors: Mbanya Jean Claude
Published: August 2003

Diabetes mellitus is now a major health problem in Africa, and patient numbers will increase with the tremendous gain in life expectancy. Africa had a population of nearly 600 million inhabitants in 1998, with an estimated diabetic population of 550 000 type 1 and 5 million type 2 diabetic patients. With the current trends, it is estimated that the African diabetic population would more than double by the year 2000 and quadruple by the year 2010. Yet the health care system of most countries in the region is geared mostly toward communicable diseases. Diabetes care is integrated in the overall national health care structures, with primary care bearing the main responsibility. Diabetic patients seek care at the primary, district, or tertiary health care systems where there are geographical disparities in the availability, organization, and quality of diabetes care. Delivery of diabetes care is fraught with problems including organizational, medical, socioeconomic, cultural, and geographic factors. Governments, diabetes associations, and other bodies comprising people affected with diabetes, physicians, nurses, nutritionists, and educators should cooperate with one another in improving diabetes care in the region.
Arsenic Tolerating Plants from Mine Sites and Hot Springs in the Semi‐Arid Region of Chihuahua, Mexico
Authors: Flores‐Tavizón E. , Alarcón‐Herrera M. T. , González‐Elizondo S. , Olguín E. J.
Published: August 2003

Phytoremediation is an emergent field of great potential for the removal of metals, metalloids and other contaminants from soil, water and sediments. The use of native plants with high tolerance and capacity to accumulate the metal to be removed is a very convenient approach. High levels of arsenic (As) have been found at several natural sources in the northern arid and semi‐arid regions of Mexico. The state of Chihuahua is, among others, one in which As has been detected in sources of natural drinking water. The aim of the present work was to identify indigenous plants in the state of Chihuahua with As tolerance and accumulating capacity. Water samples from different mine sites and hot springs were inspected. At these sites, the As concentration varied in the range of 110–191 μg/l in water and 40–2100 μg/g in soils. A native plant identified as Eleocharis sp. (Cyperaceae), collected from the nearby surroundings of a hot spring site, was found to contain an As concentration of 301 μg/g. The arsenic bioconcentration (BCF) and translocation (TF) factors for this plant exceeded 1 (5.22 and 7.37, respectively), which classifies it as an arsenic‐tolerant plant with potential use in phytoextraction. The TF of Brickellia veronicaefolia, Nicotiana glauca and Baccharis salicifolia were above one, but they had very low BCF coefficients, which limited their potential to be considered for a phytoremediation process.
Bioluminescence Biosensor for the Detection of Organomercury Contamination
Authors: Endo G. , Yamagata T. , Narita M. , Huang C.‐C.
Published: August 2003

To selectively detect organomercurial compounds in the environment, in this study a bioluminescence biosensor for organomercurials was developed using a bacterial gene expression system for the mercury resistance determinant. merB3‐Luciferase (mer‐lux) transcriptional fusion plasmids pHYΔ3Lux and pHY.Δ3Lux were constructed to evaluate the gene expression system with a new organomercury lyase gene merB3 from Bacillus megaterium strain MB1, which is resistant to a broad spectrum of mercury compounds, and with its 3'end‐deleted defective merB3, respectively. Another plasmid, pGR1A, encoding an operator/promoter sequence, merR1, merE, merT, merP and merA from the same bacterial strain was constructed and used as a transacting gene expression vector which combines the gene expression vector of mer‐lux transcriptional fusion plasmids in the same Escherichia coli cells. The transformants that carried a set of the two plasmids were used as biological sensors for the detection of organomercurials. Transformant (E. coli DH5α/pHYB3Lux, pGR1A) is available to distinguish the organomercury from inorganic mercury, since inorganic mercurials can induce the bioluminescence of both the bacterial strain lines with pHYΔB3Lux and pHYB3Lux, whereas organomercurials can only induce the bioluminescence of the lines with pHYB3Lux. These experimental results showed that the transformant with a merB3‐defective fusion plasmid, and the gene expression vector responded to only mercury chloride. On the other hand, the transformant with an intact merB3 fusion plasmid and the gene expression vector responded to mercury chloride and all organomercurials tested in the study. The sensor system responded to the existence of the phenyl mercury acetate of 50 nanomolar and was more sensitive than that of inorganic mercury (100 nanomolar). The result also indicated the capability of the system to detect bio‐affecting inorganic mercury from several hundred nanomolar to several ten micromolar.
Biological Removal of Nitrogen to Improve the Quality of Reclaimed Wastewater for Groundwater Recharge
Authors: Espino‐Valdés M. S. , Manzanares‐Papayanópoulos L. I. , Nevárez‐Moorillón G. V. , Keer‐Rendón A. , Bautista‐Margulis R.
Published: August 2003

Nitrogen removal was studied in a pilot scale continuous flow system consisting of two reactors in series for nitrification and denitrification. The system was used to eliminate ammonia, nitrate and nitrite from a secondary wastewater effluent.

The first stage of the process consisted of an aerobic upflow bioreactor with an autotrophic nitrifying population for ammonia oxidation, which was grown on silica sand granules and produced during the growth process nitrite and nitrate. During the second stage, these oxidised forms of nitrogen were successfully reduced to nitrogen gas in an anoxic denitrification fluidised bed reactor. At this stage, methanol was added as an external carbon source for the heterotrophic organisms growing on a silica sand support.

The optimum nitrification efficiency was 91% for the highest ammonia concentration at the influent (51 mg NH3‐N/l) and a retention time of 3.7 hours. With a lower ammonia concentration (23 mg NH3‐N/l), the highest nitrification efficiency was 95% corresponding to 1.1 mg NH3‐N/l in the nitrified effluent. In the denitrification process, a 95% removal efficiency of nitrite and nitrate for 55 mg NOx‐N/l at 2.3 hours and a concentration of microorganisms in the reactor of approx. 6,000 mg VSS/l was obtained. As a complementary stage of the nitrogen removal process, a silica sand and powderactivated carbon filter was installed in order to improve the quality of the final effluent in terms of other properties like turbidity, colour and the content of organic matter.
Bioprocessing of Marine Crustacean Shell Waste
Authors: Healy M. , Green A. , Healy A.
Published: August 2003

The anaerobic fermentation of waste prawn shell (Nephrops norvegicus) using lactic acid bacteria, in combination with especially selected proteolytic enzyme producing bacteria, has been established as an effective method for breaking down shell waste and isolating the valuable components contained within the shell structure. One of these components is the biopolymer chitin, which has numerous industrial applications and has traditionally been produced by a harsh chemical method which is extremely hazardous, energy consuming and ultimately damaging to the environment as it employs high concentrations of mineral acid and alkali. This qualitative study investigates the potential of prawn shell fermentation to provide a multi‐product process, thereby eliminating waste and generating revenue. Fermentations were carried out in a bench‐top, stirred tank bioreactor (5‐litres). Various components of the fermentation product were analysed. The chitinous residues were characterised by CHN and calcium analysis. The composition of the protein mixture in the fermentation liquor was assessed by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS‐PAGE). Two‐dimensional SDSPAGE followed by mass spectrometry allowed remaining proteins in the liquor to be identified. Carotenoid pigments in the liquor, potentially applicable in animal feed supplements, were investigated for their extractability in various solvents. A fine, white precipitate that is formed in the fermentation broth was also examined.

Key results of the study showed that the unique microbial mixture used in the fermentation of prawn shell waste served to achieve the desired objectives i.e. (i) the production of a purified chitin with calcium removal as high as 93.8%; (ii) the production of a pigmented liquor containing peptides, amino acids only a few intact proteins. Sarcoplasmic calcium‐binding protein was consistently found as a surviving protein in the fermentation broth. This study demonstrates the use of a biotechnological process as an alternative to the traditional chemical approach used in the manufacture of chitin. Trials have begun to assess the nutritive value of the liquor in lobster farming while biotransformation studies on bioprocessed chitin are ongoing.
Aerobic and Anaerobic Reduction of Cr(VI) by Shewanella oneidensis Effects of Cationic Metals, Sorbing Agents and Mixed Microbial Cultures
Authors: Lowe K. L. , Straube W. , Little B. , Jones‐Meehan J.
Published: August 2003

The aim of the present study was to demonstrate the loss of Cr(VI) from aqueous solutions via microbial Cr(VI) reduction. Aerobic, anaerobic and microaerophilic cultures of Shewanella oneidensis were tested for Cr(VI) reduction under a variety of conditions (i.e., various Cr(VI) concentrations, carbon sources, pH, temperature, bacterial cell densities, presence of cationic metals, sea sand, illite clay, heterologous bacteria commonly found in soil and water or the soluble electron shuttle anthraquinone 2,6 disulphonate [AQDS]). Optimum reduction of 5 mg/l Cr(VI) was observed at: pH 7, at 25–30 °C and in lactate‐amended cultures. Anaerobic cells reduced Cr(VI) at an average rate of 28 ng Cr(VI)/min × mg protein versus 13 ng Cr(VI)/min × mg protein for aerobically grown cells. The presence of cationic metals [Co(II), Ni(II)] inhibited the reduction of 50 mg/l Cr(VI) by aerobic S. oneidensis cultures but not anaerobic or microaerophilic cultures. In aerobic cultures, toxic effects due to high levels (50 mg/l) of Cr(VI) and cationic metals were alleviated by the presence of sand and illite clay particles, which sorbed Cr(VI). When 50 mg/l Ni(II) was present, more Cr(VI) was reduced by aerobic S. oneidensis cultures containing either sand or illite clay versus cultures lacking these amendments. Addition of an electron shuttle (AQDS) to the medium also enhanced 50 mg/l Cr(VI) reduction in the presence of 50 mg/l Ni(II). Cr(VI) reduction rates were similar with and without AQDS when 50 mg/l Co(II) was present. Reduction of 50 mg/l Cr(VI) was facilitated by the addition of other bacteria (Acinetobacter calcoaceticus, Pseudomonas putida and Bacillus circulans) in mixed cultures with S. oneidensis.

This study demonstrates that aerobic, anaerobic and microaerophilic cultures of S. oneidensis reduce Cr(VI). Bacterial mixtures, addition of AQDS and presence of sand or illite clay may enhance Cr(VI) reduction by this bacterium in the presence of inhibitory agents.
Bioremediation of Concrete Contaminated with n‐Hexadecane and Naphthalene
Authors: Beklemishev M. K. , Kozliak E. I.
Published: August 2003

Retention/leaching and bioremediation of n‐hexadecane and naphthalene absorbed in building grade concrete were investigated. Retention studies showed that up to 20 mg of n‐hexadecane were irreversibly absorbed per 1 g of concrete (not leached out by either water or aqueous solutions of surfactants). Bioremediation studies were conducted using three naturally occurring bacterial strains including Pseudomonas aeruginosa PG201 and soil microorganisms. Incubation of contaminated concrete pieces with bacterial suspension in shaking flasks resulted in the biodegradation/biotransformation of 8–19% of n‐hexadecane or 28–35% of naphthalene, whereas neat hydrocarbons were completely degraded. Naphthalene removal was similar with and without bacteria, and only the destination of the labelled carbon was different. Direct application of biomass on contaminated concrete (“overlay procedure”) proved to be more efficient. Up to 70–80% of n‐hexadecane and 20–55% of naphthalene (up to 80% combined with evaporation) were removed when using agar plates or filter paper with biomass. Overlay protocols using large amounts of water proved to be more efficient for the biological removal of naphthalene but detrimental for the removal of n‐hexadecane. The latter was greater with low amounts of water. Evidence obtained shows that the hydrocarbon diffusion within the pores of concrete is the rate‐limiting step for bioremediation.