A discrete Hopf fibration of S15 over S8 with S7 (unit octonions) as fibers leads to a 16D Polytope P16 with 4320 vertices obtained from the convex hull of the 16D Barnes-Wall lattice Λ16. It is argued (conjectured) ...A discrete Hopf fibration of S15 over S8 with S7 (unit octonions) as fibers leads to a 16D Polytope P16 with 4320 vertices obtained from the convex hull of the 16D Barnes-Wall lattice Λ16. It is argued (conjectured) how a subsequent 2-1 mapping (projection) of P16 onto a 8D-hyperplane might furnish the 2160 vertices of the uniform 241 polytope in 8-dimensions, and such that one can capture the chain sequence of polytopes 241,231,221,211in D=8,7,6,5dimensions, leading, respectively, to the sequence of Coxeter groups E8,E7,E6,SO(10)which are putative GUT group candidates. An embedding of the E8⊕E8and E8⊕E8⊕E8lattice into the Barnes-Wall Λ16 and Leech Λ24 lattices, respectively, is explicitly shown. From the 16D lattice E8⊕E8one can generate two separate families of Elser-Sloane 4D quasicrystals (QC’s) with H4 (icosahedral) symmetry via the “cut-and-project” method from 8D to 4D in each separate E8 lattice. Therefore, one obtains in this fashion the Cartesian product of two Elser-Sloane QC’s Q×Qspanning an 8D space. Similarly, from the 24D lattice E8⊕E8⊕E8one can generate the Cartesian product of three Elser-Sloane 4D quasicrystals (QC’s) Q×Q×Qwith H4 symmetry and spanning a 12D space.展开更多
Borrowing ideas from elliptic complex geometry, we approach M-theory compactifications on real fibrations. Precisely, we explore real toric equations rather than complex ones exploited in F-theory and related dual mod...Borrowing ideas from elliptic complex geometry, we approach M-theory compactifications on real fibrations. Precisely, we explore real toric equations rather than complex ones exploited in F-theory and related dual models. These geometries have been built by moving real toric manifolds over real bases. Using topological changing behaviors, we unveil certain data associated with gauge sectors relying on affine lie symmetries.展开更多
Using operator algebras,we extend the theory of quantum computation on a graph to a theory of computation on an arbitrary topological space.Quantum computation is usually implemented on finite discrete sets,and the pu...Using operator algebras,we extend the theory of quantum computation on a graph to a theory of computation on an arbitrary topological space.Quantum computation is usually implemented on finite discrete sets,and the purpose of this study is to extend this to theories on arbitrary sets.The conventional theory of quantum computers can be viewed as a simplified algebraic geometry theory in which the action of SU(2)is defined on each point of a discrete set.In this study,we extend this in general as a theory of quantum fibrations in which the action of the von Neumann algebra is defined on an arbitrary topological space.The quantum channel is then naturally extended as a net of von Neumann algebras.This allows for a more mathematically rigorous discussion of general theories,including physics and chemistry,which are defined on sets that are not necessarily discrete,from the perspective of quantum computer science.展开更多
In the study of the collapsed manifolds with bounded sectional curvature,the following two results provide basic tools:a(singular)fibration theorem by K.Fukaya[J.Differential Gcom.,1987.25(1):139156]and J.Cheeger,K.Fu...In the study of the collapsed manifolds with bounded sectional curvature,the following two results provide basic tools:a(singular)fibration theorem by K.Fukaya[J.Differential Gcom.,1987.25(1):139156]and J.Cheeger,K.Fukaya,and M.Gromov[J.Airier.Math.Soc.,1992.5(2):327372],and the stability for isometric compact Lie group actions on manifolds by R.S.Palais[Bull.Amer.Math.Soc.,1961,67(4):362364]and K.Grove and H.Karcher[Math.Z..1973,132:1120].The main results in this paper(partially)generalize the two results to manifolds with local bounded Ricci covering geometry.展开更多
We present a proof of the Strominger-Yau-Zaslow (SYZ) conjecture by demonstrating that mirror symmetry fundamentally represents an equivalence of computational structures between Calabi-Yau manifolds. Through developm...We present a proof of the Strominger-Yau-Zaslow (SYZ) conjecture by demonstrating that mirror symmetry fundamentally represents an equivalence of computational structures between Calabi-Yau manifolds. Through development of a rigorous quantum complexity operator formalism, we show that mirror pairs must have equivalent complexity spectra and that the SYZ fibration naturally preserves these computational invariants while implementing the required geometric transformations. Our proof proceeds by first establishing a precise mathematical framework connecting quantum complexity with geometric structures, then demonstrating that the special Lagrangian torus fibration preserves computational complexity at both local and global levels, and finally proving that this preservation necessarily implies the geometric correspondences required by the SYZ conjecture. This approach not only resolves the conjecture but reveals deeper insights about the relationship between computation and geometry in string theory. We introduce new complexity-based invariants for studying mirror symmetry and demonstrate how our framework extends naturally to related geometric structures.展开更多
Primary biliary cholangitis(PBC)is a chronic autoimmune cholestatic liver disease characterized by progressive bile duct destruction,leading to fibrosis,cirrhosis,and eventual liver failure.Over the past two decades,s...Primary biliary cholangitis(PBC)is a chronic autoimmune cholestatic liver disease characterized by progressive bile duct destruction,leading to fibrosis,cirrhosis,and eventual liver failure.Over the past two decades,significant advancements have paved the way for novel therapeutic strategies.Ursodeoxycholic acid(UDCA)has been the cornerstone of PBC management,improving survival and delaying disease progression in most patients.However,up to 40%of patients demonstrate an inadequate response to UDCA,necessitating additional treatment options.Obeticholic acid(OCA),a farnesoid X receptor agonist,has emerged as a second-line therapy,showing efficacy in reducing alkaline phosphatase levels and improving liver biochemistry.Beyond UDCA and OCA,a new wave of therapeutic agents are reshaping the PBC landscape.These include fibrates,peroxisome proliferator-activated receptor agonists and novel immunomodulatory drugs aimed at reducing autoimmune-mediated liver injury.Bile acid transport inhibitors,anti-fibrotic agents,and gut microbiome-targeted therapies are also under investigation,offering hope for personalized treatment approaches.This review highlights the evolution of PBC therapy,emphasizing the unmet needs of patients with refractory disease and the potential of emerging therapies to improve outcomes.As the therapeutic landscape continues to expand,optimizing treatment strategies through precision medicine holds the promise of transforming the management of PBC.展开更多
This paper presents a definition of residue formulas for the Euler class ot eohomology-oriented sphere fibrations ε. If the base of ε is a topological manifold, a Hopf index theorem can be obtained and, for the smoo...This paper presents a definition of residue formulas for the Euler class ot eohomology-oriented sphere fibrations ε. If the base of ε is a topological manifold, a Hopf index theorem can be obtained and, for the smooth category, a generalization of a residue formula is derived for real vector bundles given in [2].展开更多
In this series of papers, surfaces of general-type with X(O_s)=1 and fibrations of genus 2 are classified completely, and some new surfaces with invariant p_8=0 are constructed This paper will set up two kinds of nume...In this series of papers, surfaces of general-type with X(O_s)=1 and fibrations of genus 2 are classified completely, and some new surfaces with invariant p_8=0 are constructed This paper will set up two kinds of numerical Campedelli surfaces with fibrations of genus 2.展开更多
We consider base spaces of Lagrangian fibrations from singular symplectic varieties. After defining cohomologically irreducible symplectic varieties, we construct an example of Lagrar, gian fibration whose base space ...We consider base spaces of Lagrangian fibrations from singular symplectic varieties. After defining cohomologically irreducible symplectic varieties, we construct an example of Lagrar, gian fibration whose base space is isomorphic to a quotient of the projective space. We also prove that the base space of Lagrangian fibration from a cohomologically symplectic variety is isomorphic to the projective space provided that the base space is smooth.展开更多
In the medical and dental field, the importance and need for the study of materials and drugs for use as bone grafts or regeneration in injured areas due to the presence of fractures, infections or tumors that cause e...In the medical and dental field, the importance and need for the study of materials and drugs for use as bone grafts or regeneration in injured areas due to the presence of fractures, infections or tumors that cause extensive loss of bone tissue is observed. Bone is a specialized, vascularized and dynamic connective tissue that changes throughout the life of the organism. When injured, it has a unique ability to regenerate and repair without the presence of scars, but in some situations, due to the size of the defect, the bone tissue does not regenerate completely. Thus, due to its importance, there is a great development in therapeutic approaches for the treatment of bone defects through studies that include autografts, allografts and artificial materials used alone or in association with bone grafts. Pharmaceuticals composed of biomaterials and osteogenic active substances have been extensively studied because they provide potential for tissue regeneration and new strategies for the treatment of bone defects. Statins work as specific inhibitors of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMG-CoAreductase). They represent efficient drugs in lowering cholesterol, as they reduce platelet aggregation and thrombus deposition;in addition, they promote angiogenesis, reduce the β-amyloid peptide related to Alzheimer’s disease and suppress the activation of T lymphocytes. Furthermore, these substances have been used in the treatment of hypercholesterolemia and coronary artery disease. By inhibiting HMG-CoAreductase, statins not only inhibit cholesterol synthesis, but also exhibit several other beneficial pleiotropic effects. Therefore, there has been increasing interest in researching the effects of statins, including Simvastatin, on bone and osteometabolic diseases. However, statins in high doses cause inflammation in bone defects and inhibit osteoblastic differentiation, negatively contributing to bone repair. Thus, different types of studies with different concentrations of statins have been studied to positively or negatively correlate this drug with bone regeneration. In this review we will address the positive, negative or neutral effects of statins in relation to bone defects providing a comprehensive understanding of their application. Finally, we will discuss a variety of statin-based drugs and the ideal dose through a theoretical basis with preclinical, clinical and laboratory work in order to promote the repair of bone defects.展开更多
The cardioprotective effects of lipid-lowering drugs have been primarily attributed to their effects on blood lipid metabolism.However,emerging evidence indicates that lipid-lowering drugs also modulate the synthesis ...The cardioprotective effects of lipid-lowering drugs have been primarily attributed to their effects on blood lipid metabolism.However,emerging evidence indicates that lipid-lowering drugs also modulate the synthesis and secretion of adipose tissue-secreted proteins referred to as adipokines.Adipokines influence energy homeostasis and metabolism and have also been shown to modulate the vascular inflammatory cascade.The purpose of this review will be to examine the reported effects of commonly used lipid-lowering drugs(statins,fibrates,niacin and omega-3-fatty acids) on the circulating concentrations of leptin,adiponectin,tumor necrosisfactor-α(TNF-α),Retinol binding protein 4(RBP4) and resistin.Overall,the lipid-lowering drugs reviewed have minimal effects on leptin and resistin concentrations.Conversely,circulating adiponectin concentrations are consistently increased by each lipid-lowering drug reviewed with the greatest effects produced by niacin.Studies that have examined the effects of statins,niacin and omega-3-fatty acids on TNF-α demonstrate that these agents have little effect on circulating TNF-α concentrations.Niacin and fibrates appear to lower RBP4 but not resistin concentrations.The results of the available studies suggest that a strong relationship exists between pharmacological reductions in blood lipids and adiponectin that is not obvious for other adipokines reviewed.展开更多
Diabetic retinopathy affects a substantial proportion of patients with diabetes mellitus(DM) and is the leading cause of blindness in working-aged adults. Even though the incidence of diabetic retinopathy has declined...Diabetic retinopathy affects a substantial proportion of patients with diabetes mellitus(DM) and is the leading cause of blindness in working-aged adults. Even though the incidence of diabetic retinopathy has declined in the last decades, its prevalence increased and is expected to rise further as a result of the increasing incidence of type 2 DM(T2DM) and the longer life expectancy of patients with DM. The pathogenesis of diabetic retinopathy is multifactorial. Some observational studies suggested an association between dyslipidemia and the development and progression of retinopathy in patients with DM but others did not confirm this association. Regarding lipid-lowering agents, studies that evaluated the role of statins in the management of these patients are mostly small and yielded discrepant results. Large randomized studies with statins in patients with T2DM showed no benefit of these agents on diabetic retinopathy but were not designed to address this effect. In contrast, both preclinical data and two large randomized controlled studies, the FIELD and the ACCORD trial, showed that fenofibrate delays the progression of diabetic retinopathy. Even though the mechanisms underpinning this favorable effect are not entirely clear, these findings suggest that fenofibrate might represent a useful tool for the management of diabetic retinopathy.展开更多
Nonalcoholic fatty liver disease(NAFLD) is the most common chronic liver disease in developed countries and is associated not only with increased risk for liver disease-related complications but also with higher cardi...Nonalcoholic fatty liver disease(NAFLD) is the most common chronic liver disease in developed countries and is associated not only with increased risk for liver disease-related complications but also with higher cardiovascular morbidity. Accordingly, lipid-lowering agents are frequently considered in these patients to reduce cardiovascular risk. However, there have been concerns regarding the safety of these agents in patients with chronic liver diseases. In the present review, we discuss the safety of lipid-lowering agents in patients with NAFLD as well as their effects on both cardiovascular and liver disease in this population. Accumulating data suggest that statins are safe in patients with NAFLD and that they reduce the increased cardiovascular morbidity of this population. However, it is still unclear whether statins are also useful as a treatment for NAFLD per se, since there are very limited and conflicting data on their effects on liver histology. There is also very scarce evidence regarding the safety and efficacy of other lipid-lowering agents in patients with NAFLD. Randomized controlled studies are needed to evaluate the role of lipid-lowering agents and particularly statins for the prevention of both cardiovascular and liver disease-related complications in this high-risk population.展开更多
BACKGROUND Drug toxicity is a common and even serious problem in the gastrointestinal tract that is thought to be caused by a broad spectrum of agents.Although withdrawal of the causative agent would cure the disease ...BACKGROUND Drug toxicity is a common and even serious problem in the gastrointestinal tract that is thought to be caused by a broad spectrum of agents.Although withdrawal of the causative agent would cure the disease knowledge is scarce and mostly derives from case reports and series.AIM To investigate potential triggers of drug-induced colitis(DiC).METHODS We conducted a retrospective,observational case control study.Patients were assigned to DiC or one of two age-and gender-matched control groups(noninflammatory controls and inflammatory colitis of another cause)based on histopathological findings.Histopathology was reassessed in a subset of patients(28 DiC with atherosclerosis,DiC without atherosclerosis and ischaemic colitis each)for validation purposes.Medical history was collected from the electronic database and patient records.Statistical analysis included chi-squared test,t-test,logistic and multivariate regression models.RESULTS Drug-induced colitis was detected in 211 endoscopically sampled biopsy specimens of the colon mucosa(7%of all screened colonoscopic biopsy samples);a total of 633 patients were included equally matched throughout the three groups(291 males,mean age:62.1±16.1 years).In the univariate analysis,DiC was associated with diuretics,dihydropyridines,glycosides,ASS,platelet aggregation inhibitors,nonsteroidal anti-inflammatory drugs(NSAIDs),statins and fibrates,and with atherosclerosis,particularly coronary heart disease,and hyperlipoproteinaemia.Echocardiographic parameters did not show substantial differences.In the multivariate analysis only fibrates[odds ratio(OR)=9.1],NSAIDs(OR=6.7)and atherosclerosis(OR=2.1)proved to be associated with DiC.Both DiC reassessment groups presented milder inflammation than ischaemic colitis.The DiC patients with atherosclerosis exhibited histological features from both DiC without atherosclerosis and ischaemic colitis.CONCLUSION Several drugs indicated for the treatment of cardiovascular and related diseases are associated with DiC.Atherosclerosis and microcirculatory disturbances seem to play an important pathogenetic role.展开更多
文摘A discrete Hopf fibration of S15 over S8 with S7 (unit octonions) as fibers leads to a 16D Polytope P16 with 4320 vertices obtained from the convex hull of the 16D Barnes-Wall lattice Λ16. It is argued (conjectured) how a subsequent 2-1 mapping (projection) of P16 onto a 8D-hyperplane might furnish the 2160 vertices of the uniform 241 polytope in 8-dimensions, and such that one can capture the chain sequence of polytopes 241,231,221,211in D=8,7,6,5dimensions, leading, respectively, to the sequence of Coxeter groups E8,E7,E6,SO(10)which are putative GUT group candidates. An embedding of the E8⊕E8and E8⊕E8⊕E8lattice into the Barnes-Wall Λ16 and Leech Λ24 lattices, respectively, is explicitly shown. From the 16D lattice E8⊕E8one can generate two separate families of Elser-Sloane 4D quasicrystals (QC’s) with H4 (icosahedral) symmetry via the “cut-and-project” method from 8D to 4D in each separate E8 lattice. Therefore, one obtains in this fashion the Cartesian product of two Elser-Sloane QC’s Q×Qspanning an 8D space. Similarly, from the 24D lattice E8⊕E8⊕E8one can generate the Cartesian product of three Elser-Sloane 4D quasicrystals (QC’s) Q×Q×Qwith H4 symmetry and spanning a 12D space.
文摘Borrowing ideas from elliptic complex geometry, we approach M-theory compactifications on real fibrations. Precisely, we explore real toric equations rather than complex ones exploited in F-theory and related dual models. These geometries have been built by moving real toric manifolds over real bases. Using topological changing behaviors, we unveil certain data associated with gauge sectors relying on affine lie symmetries.
基金supported by Pacific Institute for the Mathematical Science(PIMS)postdoctoral fellowship award and by the U.S.Department of Energy,Office of Science,National Quantum Information Science Research Centers,Co-design Center for Quantum Advantage(C2QA)under Contract No.DESC0012704。
文摘Using operator algebras,we extend the theory of quantum computation on a graph to a theory of computation on an arbitrary topological space.Quantum computation is usually implemented on finite discrete sets,and the purpose of this study is to extend this to theories on arbitrary sets.The conventional theory of quantum computers can be viewed as a simplified algebraic geometry theory in which the action of SU(2)is defined on each point of a discrete set.In this study,we extend this in general as a theory of quantum fibrations in which the action of the von Neumann algebra is defined on an arbitrary topological space.The quantum channel is then naturally extended as a net of von Neumann algebras.This allows for a more mathematically rigorous discussion of general theories,including physics and chemistry,which are defined on sets that are not necessarily discrete,from the perspective of quantum computer science.
文摘In the study of the collapsed manifolds with bounded sectional curvature,the following two results provide basic tools:a(singular)fibration theorem by K.Fukaya[J.Differential Gcom.,1987.25(1):139156]and J.Cheeger,K.Fukaya,and M.Gromov[J.Airier.Math.Soc.,1992.5(2):327372],and the stability for isometric compact Lie group actions on manifolds by R.S.Palais[Bull.Amer.Math.Soc.,1961,67(4):362364]and K.Grove and H.Karcher[Math.Z..1973,132:1120].The main results in this paper(partially)generalize the two results to manifolds with local bounded Ricci covering geometry.
文摘We present a proof of the Strominger-Yau-Zaslow (SYZ) conjecture by demonstrating that mirror symmetry fundamentally represents an equivalence of computational structures between Calabi-Yau manifolds. Through development of a rigorous quantum complexity operator formalism, we show that mirror pairs must have equivalent complexity spectra and that the SYZ fibration naturally preserves these computational invariants while implementing the required geometric transformations. Our proof proceeds by first establishing a precise mathematical framework connecting quantum complexity with geometric structures, then demonstrating that the special Lagrangian torus fibration preserves computational complexity at both local and global levels, and finally proving that this preservation necessarily implies the geometric correspondences required by the SYZ conjecture. This approach not only resolves the conjecture but reveals deeper insights about the relationship between computation and geometry in string theory. We introduce new complexity-based invariants for studying mirror symmetry and demonstrate how our framework extends naturally to related geometric structures.
文摘Primary biliary cholangitis(PBC)is a chronic autoimmune cholestatic liver disease characterized by progressive bile duct destruction,leading to fibrosis,cirrhosis,and eventual liver failure.Over the past two decades,significant advancements have paved the way for novel therapeutic strategies.Ursodeoxycholic acid(UDCA)has been the cornerstone of PBC management,improving survival and delaying disease progression in most patients.However,up to 40%of patients demonstrate an inadequate response to UDCA,necessitating additional treatment options.Obeticholic acid(OCA),a farnesoid X receptor agonist,has emerged as a second-line therapy,showing efficacy in reducing alkaline phosphatase levels and improving liver biochemistry.Beyond UDCA and OCA,a new wave of therapeutic agents are reshaping the PBC landscape.These include fibrates,peroxisome proliferator-activated receptor agonists and novel immunomodulatory drugs aimed at reducing autoimmune-mediated liver injury.Bile acid transport inhibitors,anti-fibrotic agents,and gut microbiome-targeted therapies are also under investigation,offering hope for personalized treatment approaches.This review highlights the evolution of PBC therapy,emphasizing the unmet needs of patients with refractory disease and the potential of emerging therapies to improve outcomes.As the therapeutic landscape continues to expand,optimizing treatment strategies through precision medicine holds the promise of transforming the management of PBC.
基金Project supported by the DGICYT Grant (No. MTM2007-60016)the Junta de Andalucía Grant(No. P07-FQM-2863)
文摘This paper presents a definition of residue formulas for the Euler class ot eohomology-oriented sphere fibrations ε. If the base of ε is a topological manifold, a Hopf index theorem can be obtained and, for the smooth category, a generalization of a residue formula is derived for real vector bundles given in [2].
文摘In this series of papers, surfaces of general-type with X(O_s)=1 and fibrations of genus 2 are classified completely, and some new surfaces with invariant p_8=0 are constructed This paper will set up two kinds of numerical Campedelli surfaces with fibrations of genus 2.
基金supported by Japan Society for Promotion of Sciences(Grant No.18684001)
文摘We consider base spaces of Lagrangian fibrations from singular symplectic varieties. After defining cohomologically irreducible symplectic varieties, we construct an example of Lagrar, gian fibration whose base space is isomorphic to a quotient of the projective space. We also prove that the base space of Lagrangian fibration from a cohomologically symplectic variety is isomorphic to the projective space provided that the base space is smooth.
文摘In the medical and dental field, the importance and need for the study of materials and drugs for use as bone grafts or regeneration in injured areas due to the presence of fractures, infections or tumors that cause extensive loss of bone tissue is observed. Bone is a specialized, vascularized and dynamic connective tissue that changes throughout the life of the organism. When injured, it has a unique ability to regenerate and repair without the presence of scars, but in some situations, due to the size of the defect, the bone tissue does not regenerate completely. Thus, due to its importance, there is a great development in therapeutic approaches for the treatment of bone defects through studies that include autografts, allografts and artificial materials used alone or in association with bone grafts. Pharmaceuticals composed of biomaterials and osteogenic active substances have been extensively studied because they provide potential for tissue regeneration and new strategies for the treatment of bone defects. Statins work as specific inhibitors of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMG-CoAreductase). They represent efficient drugs in lowering cholesterol, as they reduce platelet aggregation and thrombus deposition;in addition, they promote angiogenesis, reduce the β-amyloid peptide related to Alzheimer’s disease and suppress the activation of T lymphocytes. Furthermore, these substances have been used in the treatment of hypercholesterolemia and coronary artery disease. By inhibiting HMG-CoAreductase, statins not only inhibit cholesterol synthesis, but also exhibit several other beneficial pleiotropic effects. Therefore, there has been increasing interest in researching the effects of statins, including Simvastatin, on bone and osteometabolic diseases. However, statins in high doses cause inflammation in bone defects and inhibit osteoblastic differentiation, negatively contributing to bone repair. Thus, different types of studies with different concentrations of statins have been studied to positively or negatively correlate this drug with bone regeneration. In this review we will address the positive, negative or neutral effects of statins in relation to bone defects providing a comprehensive understanding of their application. Finally, we will discuss a variety of statin-based drugs and the ideal dose through a theoretical basis with preclinical, clinical and laboratory work in order to promote the repair of bone defects.
基金Supported by Boshell Diabetes and Metabolic Diseases Research Program
文摘The cardioprotective effects of lipid-lowering drugs have been primarily attributed to their effects on blood lipid metabolism.However,emerging evidence indicates that lipid-lowering drugs also modulate the synthesis and secretion of adipose tissue-secreted proteins referred to as adipokines.Adipokines influence energy homeostasis and metabolism and have also been shown to modulate the vascular inflammatory cascade.The purpose of this review will be to examine the reported effects of commonly used lipid-lowering drugs(statins,fibrates,niacin and omega-3-fatty acids) on the circulating concentrations of leptin,adiponectin,tumor necrosisfactor-α(TNF-α),Retinol binding protein 4(RBP4) and resistin.Overall,the lipid-lowering drugs reviewed have minimal effects on leptin and resistin concentrations.Conversely,circulating adiponectin concentrations are consistently increased by each lipid-lowering drug reviewed with the greatest effects produced by niacin.Studies that have examined the effects of statins,niacin and omega-3-fatty acids on TNF-α demonstrate that these agents have little effect on circulating TNF-α concentrations.Niacin and fibrates appear to lower RBP4 but not resistin concentrations.The results of the available studies suggest that a strong relationship exists between pharmacological reductions in blood lipids and adiponectin that is not obvious for other adipokines reviewed.
文摘Diabetic retinopathy affects a substantial proportion of patients with diabetes mellitus(DM) and is the leading cause of blindness in working-aged adults. Even though the incidence of diabetic retinopathy has declined in the last decades, its prevalence increased and is expected to rise further as a result of the increasing incidence of type 2 DM(T2DM) and the longer life expectancy of patients with DM. The pathogenesis of diabetic retinopathy is multifactorial. Some observational studies suggested an association between dyslipidemia and the development and progression of retinopathy in patients with DM but others did not confirm this association. Regarding lipid-lowering agents, studies that evaluated the role of statins in the management of these patients are mostly small and yielded discrepant results. Large randomized studies with statins in patients with T2DM showed no benefit of these agents on diabetic retinopathy but were not designed to address this effect. In contrast, both preclinical data and two large randomized controlled studies, the FIELD and the ACCORD trial, showed that fenofibrate delays the progression of diabetic retinopathy. Even though the mechanisms underpinning this favorable effect are not entirely clear, these findings suggest that fenofibrate might represent a useful tool for the management of diabetic retinopathy.
文摘Nonalcoholic fatty liver disease(NAFLD) is the most common chronic liver disease in developed countries and is associated not only with increased risk for liver disease-related complications but also with higher cardiovascular morbidity. Accordingly, lipid-lowering agents are frequently considered in these patients to reduce cardiovascular risk. However, there have been concerns regarding the safety of these agents in patients with chronic liver diseases. In the present review, we discuss the safety of lipid-lowering agents in patients with NAFLD as well as their effects on both cardiovascular and liver disease in this population. Accumulating data suggest that statins are safe in patients with NAFLD and that they reduce the increased cardiovascular morbidity of this population. However, it is still unclear whether statins are also useful as a treatment for NAFLD per se, since there are very limited and conflicting data on their effects on liver histology. There is also very scarce evidence regarding the safety and efficacy of other lipid-lowering agents in patients with NAFLD. Randomized controlled studies are needed to evaluate the role of lipid-lowering agents and particularly statins for the prevention of both cardiovascular and liver disease-related complications in this high-risk population.
文摘BACKGROUND Drug toxicity is a common and even serious problem in the gastrointestinal tract that is thought to be caused by a broad spectrum of agents.Although withdrawal of the causative agent would cure the disease knowledge is scarce and mostly derives from case reports and series.AIM To investigate potential triggers of drug-induced colitis(DiC).METHODS We conducted a retrospective,observational case control study.Patients were assigned to DiC or one of two age-and gender-matched control groups(noninflammatory controls and inflammatory colitis of another cause)based on histopathological findings.Histopathology was reassessed in a subset of patients(28 DiC with atherosclerosis,DiC without atherosclerosis and ischaemic colitis each)for validation purposes.Medical history was collected from the electronic database and patient records.Statistical analysis included chi-squared test,t-test,logistic and multivariate regression models.RESULTS Drug-induced colitis was detected in 211 endoscopically sampled biopsy specimens of the colon mucosa(7%of all screened colonoscopic biopsy samples);a total of 633 patients were included equally matched throughout the three groups(291 males,mean age:62.1±16.1 years).In the univariate analysis,DiC was associated with diuretics,dihydropyridines,glycosides,ASS,platelet aggregation inhibitors,nonsteroidal anti-inflammatory drugs(NSAIDs),statins and fibrates,and with atherosclerosis,particularly coronary heart disease,and hyperlipoproteinaemia.Echocardiographic parameters did not show substantial differences.In the multivariate analysis only fibrates[odds ratio(OR)=9.1],NSAIDs(OR=6.7)and atherosclerosis(OR=2.1)proved to be associated with DiC.Both DiC reassessment groups presented milder inflammation than ischaemic colitis.The DiC patients with atherosclerosis exhibited histological features from both DiC without atherosclerosis and ischaemic colitis.CONCLUSION Several drugs indicated for the treatment of cardiovascular and related diseases are associated with DiC.Atherosclerosis and microcirculatory disturbances seem to play an important pathogenetic role.
