Abstract:
:The smooth muscle of the normal bladder wall must have some specific properties. It must be very compliant and able to reorganise itself during filling and emptying to accommodate the change in volume without generating any intravesical pressure, but whilst maintaining the normal shape of the bladder. It must be capable of synchronous activation to generate intravesical pressure at any length to allow voiding. The cells achieve this through spontaneous electrical activity combined with poor electrical coupling between cells, and a dense excitatory innervation. In the diseased state, alterations of the smooth muscle may lead to failure to store or failure to empty properly. The diseased states discussed are bladder instability and diabetic neuropathy. Bladder instability is characterised urodynamically by uninhibitable rises in pressure during filling, and is seen idiopathically and in association with bladder outflow obstruction and neuropathy. In diabetic neuropathy, many of the smooth muscle changes are a consequence of diuresis, but there is evidence for alterations in the sensory arm of the micturition reflex. In the unstable bladder, additional alterations of the smooth muscle are seen, which are probably caused by the patchy denervation that occurs. The causes of this denervation are not fully established. Nonsurgical treatment of instability is not yet satisfactory; neuromodulation has some promise, but is expensive, and the mechanisms poorly understood. Pharmacological treatment is largely through muscarinic receptor blockade. Drugs to reduce the excitability of the smooth muscle are being sought, since they may represent a better pharmacological option.
journal_name
Pharmacol Therjournal_title
Pharmacology & therapeuticsauthors
Turner WH,Brading AFdoi
10.1016/s0163-7258(97)00038-7subject
Has Abstractpub_date
1997-08-01 00:00:00pages
77-110issue
2eissn
0163-7258issn
1879-016Xpii
S0163-7258(97)00038-7journal_volume
75pub_type
杂志文章,评审abstract::The small heat shock proteins (HSPs) HSP20, HSP27 and alphaB-crystallin are chaperone proteins that are abundantly expressed in smooth muscles are important modulators of muscle contraction, cell migration and cell survival. This review focuses on factors regulating expression of small HSPs in smooth muscle, signaling...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2008.04.005
更新日期:2008-07-01 00:00:00
abstract::During the last 20 years, an expanding body of research has elucidated the central role of amyloid precursor protein (APP) processing and amyloid beta peptide (Abeta) production in the risk, onset, and progression of the neurodegenerative disorder Alzheimer's disease (AD), the most common form of dementia. Ongoing res...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2007.06.006
更新日期:2007-11-01 00:00:00
abstract::This review focuses on the chemical and enzymatic aspects of the reductive activation of mitomycin C, its disulfide analogs KW-2149 and BMS-181174, and, in less detail, FR66979 and FR900482, newly discovered antitumor antibiotics related to mitomycins. Furthermore, structural aspects of DNA damage induced by these dru...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0163-7258(97)00088-0
更新日期:1997-10-01 00:00:00
abstract::This article reviews the experimental data that points to formation of reactive oxygen species (ROS) and oxidative DNA base damage as being important contributors to cancer development. Particular emphasis is placed on the role they play in genetic changes occurring during tumor promotion. A number of structurally dif...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/0163-7258(92)90047-4
更新日期:1992-01-01 00:00:00
abstract::The purpose of this paper is to provide an integrative review and offer novel insights regarding human research with classic psychedelics (classic hallucinogens), which are serotonin 2A receptor (5-HT2AR) agonists such as lysergic acid diethylamide (LSD), mescaline, and psilocybin. Classic psychedelics have been admin...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2018.11.010
更新日期:2019-05-01 00:00:00
abstract::The chewing of the stimulant leaf khat is a habit that is widespread in certain countries of East Africa and the Arabian peninsula. During the last decade, important progress has been made in understanding the pharmacological basis for the effects of khat. It is now known that the CNS action of this drug is due to the...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/0163-7258(90)90057-9
更新日期:1990-01-01 00:00:00
abstract::Cardiovascular diseases cause more mortality and morbidity worldwide than any other diseases. Although many intracellular signaling pathways influence cardiac physiology and pathology, the mitogen-activated protein kinase (MAPK) family has garnered significant attention because of its vast implications in signaling an...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2014.05.013
更新日期:2014-11-01 00:00:00
abstract::For decades, intensive studies have attempted to identify the mechanisms underlying malignant tumor growth. Despite significant progress, most therapeutic approaches fail to eliminate all tumor cells. The remaining tumor cells often result in recurrence and metastasis. Recently, the idea of a cancer stem cell was prop...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2008.04.008
更新日期:2008-07-01 00:00:00
abstract::Mesenchymal stem cells (MSCs) are multipotent tissue stem cells that differentiate into a number of mesodermal tissue types, including osteoblasts, adipocytes, chondrocytes and myofibroblasts. MSCs were originally identified in the bone marrow (BM) of humans and other mammals, but recent studies have shown that they a...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2019.04.005
更新日期:2019-08-01 00:00:00
abstract::The developing lung is highly susceptible to damage from exposure to environmental toxicants particularly due to the protracted maturation of the respiratory system, extending from the embryonic phase of development in utero through to adolescence. The functional organization of the lungs requires a coordinated ontoge...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2007.01.011
更新日期:2007-05-01 00:00:00
abstract::Mammals dispose of cholesterol mainly through 7alpha-hydroxylated bile acids, and the enzyme catalyzing the 7alpha-hydroxylation, cholesterol 7alpha-hydroxylase (CYP7A1), has a deep impact on cholesterol homeostasis. In this review, we present the study of regulation of CYP7A1 as a good exemplification of the extraord...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2007.08.003
更新日期:2007-12-01 00:00:00
abstract::Arthritis is a chronic disease of joints. It is highly prevalent, particularly in the elderly, and is commonly associated with pain that interferes with quality of life. Because of its chronic nature, pharmacological approaches to pain relief and joint repair must be safe for long term use, a quality many current ther...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2018.02.015
更新日期:2018-07-01 00:00:00
abstract::Hepatic methionine adenosyltransferase (MAT) deficiency is caused by mutations in the human MAT1A gene that abolish or reduce hepatic MAT activity that catalyzes the synthesis of S-adenosylmethionine from methionine and ATP. This genetic disorder is characterized by isolated persistent hypermethioninemia in the absenc...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0163-7258(99)00047-9
更新日期:2000-01-01 00:00:00
abstract::Evidence from experimental and clinical studies suggests the involvement of the endogenous opioid system in several neurologic and psychiatric disorders (Alzheimer's, Huntington's and Parkinson's diseases, drug-induced movement disorders, Gilles de la Tourette syndrome, stroke, ischemia, brain and spinal cord injury, ...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/0163-7258(90)90026-x
更新日期:1990-01-01 00:00:00
abstract::Although the existence of halogenated lipids in lower organisms has been known for many years, it is only since the 1990s that interest in their occurrence in mammalian systems has developed. Chlorinated (and other halogenated) lipids can arise from oxidation by hypohalous acids, such as HOCl, which are products of th...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2007.06.002
更新日期:2007-09-01 00:00:00
abstract::Thoracic aortic aneurysms (TAAs) are a potential life-threatening disease with limited pharmacological treatment options. Current treatment options are aimed at lowering aortic hemodynamic stress, predominantly with β-adrenoceptor blockers. Increasing evidence supports a role for the renin-angiotensin system (RAS) in ...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2011.04.002
更新日期:2011-07-01 00:00:00
abstract::Liver parenchyma shows a remarkable heterogeneity of the hepatocytes along the porto-central axis with respect to ultrastructure and enzyme activities resulting in different cellular functions within different zones of the liver lobuli. According to the concept of metabolic zonation, the spatial organization of the va...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/0163-7258(92)90055-5
更新日期:1992-01-01 00:00:00
abstract::gamma-Aminobutyric acid (GABA)A receptors for the inhibitory neurotransmitter GABA are likely to be found on most, if not all, neurons in the brain and spinal cord. They appear to be the most complicated of the superfamily of ligand-gated ion channels in terms of the large number of receptor subtypes and also the vari...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/0163-7258(95)02043-8
更新日期:1996-01-01 00:00:00
abstract::Nucleoside monophosphate kinases catalyze the reversible phosphotransferase reaction between nucleoside triphosphates and monophosphates, i.e., monophosphates are converted to their corresponding diphosphate form. These enzymes play an important role in the synthesis of nucleotides that are required for a variety of c...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0163-7258(00)00048-6
更新日期:2000-08-01 00:00:00
abstract::Artemisinins are a unique class of antimalarial drugs with significant potential for drug repurposing for a wide range of diseases including cancer. Cancer is a leading cause of death globally and the majority of cancer related deaths occur in Low and Middle Income Countries (LMICs) where conventional treatment option...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2020.107706
更新日期:2020-12-01 00:00:00
abstract::Initially regarded as "epigenetic modifiers" acting predominantly through chromatin remodeling via histone acetylation, HDACIs, alternatively referred to as lysine deacetylase or simply deacetylase inhibitors, have since been recognized to exert multiple cytotoxic actions in cancer cells, often through acetylation of ...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2014.04.004
更新日期:2014-09-01 00:00:00
abstract::Considering both cancer's serious impact on public health and the side effects of cancer treatments, strategies towards targeted cancer therapy have lately gained considerable interest. Employment of gold nanoparticles (GNPs), in combination with ionizing and non-ionizing radiations, has been shown to improve the effe...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2017.03.006
更新日期:2017-10-01 00:00:00
abstract::Decades of research have established that the biological functions of thyrotropin-releasing hormone (TRH) extend far beyond its role as a regulator of the hypothalamic-pituitary-thyroid axis. Gary et al. [Gary, K.A., Sevarino, K.A., Yarbrough, G.G., Prange, A.J. Jr., Winokur, A. (2003). The thyrotropin-releasing hormo...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2008.09.004
更新日期:2009-01-01 00:00:00
abstract::The past three decades have witnessed a welcome expansion of the therapeutic armamentarium for the management of pulmonary arterial hypertension (PAH). However, against this backdrop, there have been some notable disappointments in drug development. Here we use these as case studies to emphasize the importance of info...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2016.04.012
更新日期:2016-08-01 00:00:00
abstract::Macrovascular complications of diabetes, including diabetic cardiovascular disease (CVD), occur through a number of hyperglycaemia-induced mechanisms that include generation of oxidative stress, accumulation of advanced glycation end-products (AGE) and activation of protein kinase C (PKC). Cardiac oxidative stress is ...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2016.11.013
更新日期:2017-04-01 00:00:00
abstract::Unwanted cells are removed by physiological cell death processes that are highly conserved throughout the animal kingdom. Physiological cell death plays an important role in development, tissue homeostasis and defence against viral infection and mutation. This review describes the molecular components that implement t...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0163-7258(96)00098-8
更新日期:1996-01-01 00:00:00
abstract::Osteoporosis is defined as a progressive systemic skeletal disease characterised by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. The clinical relevance of osteoporosis derives from the fractures that it produces. More th...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0163-7258(02)00164-x
更新日期:2002-01-01 00:00:00
abstract::Hypertension is associated with immune cells activation and their migration into the kidney, vasculature, heart and brain. These inflammatory mechanisms are critical for blood pressure regulation and mediate target organ damage, creating unique novel targets for pharmacological modulation. In response to angiotensin I...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2020.107799
更新日期:2020-12-24 00:00:00
abstract::Diabetes is a debilitating disease characterized by chronic hyperglycemia and is often associated with obesity. With diabetes and obesity incidence on the rise, it is imperative to develop novel therapeutics that will not only lower blood glucose levels, but also combat the associated obesity. The G protein-coupled re...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2012.05.009
更新日期:2012-09-01 00:00:00
abstract::G protein-coupled receptors (GPCR) interact not only with heterotrimeric G proteins but also with accessory proteins called GPCR interacting proteins (GIP). These proteins have important functions. They are implicated in GPCR targeting to specific cellular compartments, in their assembling into large functional comple...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2004.06.004
更新日期:2004-09-01 00:00:00