Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Caffeine, widely consumed in beverages, and many xanthine analogs have had a major impact on biomedical research. Caffeine and various analogs, the latter designed to enhance potency and selectivity toward specific biological targets, have played key roles in defining the nature and role of adenosine receptors, phosphodiesterases, and calcium release channels in physiological processes. Such xanthines and other caffeine-inspired heterocycles now provide important research tools and potential therapeutic agents for intervention in Alzheimer's disease, asthma, cancer, diabetes, and Parkinson's disease. Such compounds also have activity as analgesics, antiinflammatories, antitussives, behavioral stimulants, diuretics/natriuretics, and lipolytics. Adverse effects can include anxiety, hypertension, certain drug interactions, and withdrawal symptoms.
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PMID:Caffeine analogs: biomedical impact. 1751 58

The aim of this study is to describe, from the perspective of general practitioners, the role of relatives and caregivers who accompany a patient in their consultation and treatment processes. 435 general practitioners filled out two questionnaires: the first was self administered and the second described specific clinical situations and the possible role of the family caregiver in the case of a patient with Alzheimer's diseases, Parkinson's disease, depression, epilepsy, asthma, cardiovascular disease, or type II diabetes. General practitioners think that overall they offer satisfactory responses to relatives' requests and concerns regarding the disease itself and its treatment. However, they do not feel skilled or qualified enough to answer them with regard to administrative or social questions. The relative's role is for the most part, perceived as positive, and seems to contribute to the efficacy of the care provided. This description corresponds to a new trend in modern medical practice, dominated by the burden of chronic and disabling diseases which implies, and in some cases requires, the need to involve a relative's presence and on-going support.
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PMID:[Perspectives of general practitioners on the role of patients' caregivers in the process of consultation and treatment]. 1770 88

Reactive oxygen species (ROS) play an important role in the pathogenesis of airway inflammation and hyperresponsiveness. Recent studies have demonstrated that antioxidants are able to reduce airway inflammation and hyperreactivity in animal models of allergic airway disease. A newly developed antioxidant, small molecular weight thiol compound, N-acetylcysteine amide (AD4) has been shown to increase cellular levels of glutathione and to attenuate oxidative stress related disorders such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. However, the effects of AD4 on allergic airway disease such as asthma are unknown. We used ovalbumin (OVA)-inhaled mice to evaluate the role of AD4 in allergic airway disease. In this study with OVA-inhaled mice, the increased ROS generation, the increased levels of Th2 cytokines and VEGF, the increased vascular permeability, the increased mucus production, and the increased airway resistance in the lungs were significantly reduced by the administration of AD4. We also found that the administration of AD4 decreased the increases of the NF-kappaB and hypoxia-inducible factor-1alpha (HIF-1alpha) levels in nuclear protein extracts of lung tissues after OVA inhalation. These results suggest that AD4 attenuates airway inflammation and hyperresponsiveness by regulating activation of NF-kappaB and HIF-1alpha as well as reducing ROS generation in allergic airway disease.
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PMID:A novel thiol compound, N-acetylcysteine amide, attenuates allergic airway disease by regulating activation of NF-kappaB and hypoxia-inducible factor-1alpha. 1816 Aug 46

Statins are pluripotent agents exhibiting multiple non-lipid-lowering actions. Besides their established role in the management of hypercholesterolemia, statins may also have beneficial actions in other pathological conditions, namely: a) osteoporosis and osteoporosis-related bone fractures, b) cancer, c) solid organ transplantation, d) cerebrovascular events (transient ischemic attack and stroke episodes), e) various neurological disorders, such as Alzheimer's disease, Parkinson's disease and multiple sclerosis, f) cardiac arrhythmias and heart failure, g) renal diseases, h) rheumatoid arthritis, i) autoimmune diseases, j) sepsis, and k) allergic asthma. We reviewed the literature searching for studies that support or oppose the use of statins in each proposed indication. In some of these emerging indications, a role for statin treatment is more firmly set; for others, current evidence is more controversial. Future trials may reveal more convincing evidence that will make statin use necessary in the therapeutic management of several diseases.
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PMID:Emerging indications for statins: a pluripotent family of agents with several potential applications. 1822 Jul 99

Tetracycline and its derivatives, such as chlortetracycline, oxytetracycline, minocycline, doxycycline, methacycline and lymecycline, are naturally occurring or semi-synthetic polyketide compounds that exhibit a well known broad-spectrum antibacterial activity that interferes with prokaryotic protein synthesis at the ribosome level. In addition to this well known antibacterial activity these compounds also exhibit a variety of additional, less well known properties. Among them are separate and distinct anti-inflammatory properties. Tetracycline and related compounds have been shown to be effective chemotherapeutic agents in a wide variety of chronic inflammatory diseases and conditions. These include periodontitis, rosacea, acne, auto-immune diseases such as rheumatoid arthritis and protection of the central nervous system against trauma and neurodegenerative diseases such as stroke, multiple sclerosis and Parkinson disease. Tetracycline and related compounds appear to be beneficial for treatment of several chronic inflammatory airway diseases. Among them are asthma, bronchiectasis, acute respiratory distress syndrome, chemical induced lung damage and cystic fibrosis. The clinical use of tetracycline-type drugs in treatment of chronic airway inflammation is becoming a topic of intense interest. Recent findings in this area have led to an understanding of the myriad physiological, cellular and molecular mechanisms of the inflammatory response and how this response may be controlled to limit damage to host cells and tissues. This review presents a brief summary of the recent research in the area of tetracycline and its derivatives in control of pulmonary inflammation.
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PMID:Tetracyclines and pulmonary inflammation. 1822 Sep 43

The role of Helicobacter pylori (HP) in some digestive diseases (gastritis, ulcer, gastric cancer, MALT lymphoma) is well known. It has been suggested relatively recently that infection with HP can be involved in various extra-digestive conditions: respiratory disorders (chronic obstructive pulmonary disease, bronchiectasis, lung cancer, pulmonary tuberculosis, bronchial asthma); vascular disorders (ischaemic heart disease, stroke, primary Raynaud phenomena, primary headache); autoimmune disorders (Sjogren syndrome, Henoch-Schonlein purpura, autoimmune thrombocytopenia, autoimmune thyroiditis, Parkinson's disease, idiopathic chronic urticaria, rosacea, alopecia areata); other disorders (iron deficiency anaemia, growth retardations, liver cirrhosis). Case studies, small patient series and non-randomized trials that have shown a beneficial effect of HP eradication in different conditions are not convincing. According to Mastricht III the only conditions where HP eradication is indicated are immune thrombocytopenic purpura and iron deficiency anaemia.
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PMID:Extragastric manifestations of Helicobacter pylori infection. 1829 84

The cyclic nucleotide phosphodiesterases (PDEs) are intracellular enzymes that catalyze the hydrolysis of 3,'5'-cyclic nucleotides, such as cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), to their corresponding 5'nucleotide monophosphates. These enzymes play an important role in controlling cellular concentrations of cyclic nucleotides and thus regulate a variety of cellular signaling events. PDEs are emerging as drug targets for several diseases, including asthma, cardiovascular disease, attention-deficit hyperactivity disorder, Parkinson's disease, and Alzheimer's disease. Although biochemical assays with purified recombinant PDE enzymes and cAMP or cGMP substrate are commonly used for compound screening, cell-based assays would provide a better assessment of compound activity in a more physiological context. The authors report the development and validation of a new cell-based PDE4 assay using a constitutively active G-protein-coupled receptor as a driving force for cAMP production and a cyclic nucleotide-gated cation channel as a biosensor in 1536-well plates.
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PMID:A cell-based PDE4 assay in 1536-well plate format for high-throughput screening. 1859 13

Prokinetic agents are effective not only for disease of the gastrointestinal (GI) tract but also for those external to the GI tract such as the central nervous system, and the respiratory, urologic, and metabolic organs. This article reviews the effectiveness of prokinetic agents against diseases external to the GI tract. Studies were identified by computerized and manual searches of the available literature. A Medline search was performed (1975-July, 2008) using the following medical subject headings: prokinetic agent, metoclopramide, domperidone, trimebutine, cisapride, itopride, mosapride, tegaserod, and human. The identified diseases for which prokinetic agents may be effective are various: bronchial asthma, chronic cough, hiccup, spontaneous bacterial peritonitis, cholelithiasis, diabetes mellitus, acute migraine, Parkinson's disease, anorexia nervosa, Tourette's disorder, urologic sequelae of spinal cord injury and of radical hysterectomy for cervical cancer, laryngeal dysfunction and so on. These agents are also useful for prevention of aspiration pneumonia during anesthesia, and in tube-fed patients. Prokinetic agents should be a valuable addition to our currently limited pharmacological armamentarium not only for functional bowel disease, but also for diseases external to the GI tract.
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PMID:Effectiveness of prokinetic agents against diseases external to the gastrointestinal tract. 1922 Jun 73

Indiscriminately suppressing total c-Jun N-terminal kinase (JNK) activity is not an appropriate strategy because each JNK appears to have a distinct function in cancer, asthma, diabetes, or Parkinson's disease. Herein, we report that 7-(6-N-phenylaminohexyl)amino-2H-anthra[1,9-cd]pyrazol-6-one (AV-7) inhibited JNK1 activity, but not JNK2 or JNK3. We found that ultraviolet B (UVB) induced c-Jun phosphorylation and sub-G1 accumulation in JNK2(-/-) murine embryonic fibroblasts, which contain an abundance of JNK1, but not JNK2. These results demonstrate that AV-7 is an isoform selective small-molecule inhibitor of JNK1 activity, which might be developed as a therapeutic against diabetes.
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PMID:A selective small-molecule inhibitor of c-Jun N-terminal kinase 1. 1952 17

The adenosine receptors (A(1), A(2A), A(2B) and A(3)) are important and ubiquitous mediators of cellular signalling, which play vital roles in protecting tissues and organs from damage. Launched drugs include the adenosine receptor antagonists theophylline and doxofylline (both used as bronchodilators in respiratory disorders such as asthma), while several compounds are presently in clinical trials for a range of indications, including heart failure, Parkinson's disease, rheumatoid arthritis, cancer, pain and chronic obstructive pulmonary disease. A host of companies and institutions are addressing the huge potential for the development of selective adenosine receptor agonists and antagonists, so that it appears we are on the verge of a new wave of compounds approaching the market for many unmet medical needs. This review presents an analysis of the patenting activity in the area for 2006 and an interpretation and reflection on the developments that we can expect in the future.
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PMID:Therapeutic potential of adenosine receptor antagonists and agonists. 2014 84


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