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Sample records for drug induced parkinsonism

  1. DAT imaging in drug-induced and psychogenic parkinsonism.

    PubMed

    Tolosa, Eduardo; Coelho, Miguel; Gallardo, Marisol

    2003-10-01

    Parkinson's syndrome (PS) is frequently encountered in disorders associated with prominent degeneration of the nigrostriatal pathway as in Parkinson's disease, multisystem atrophy, and progressive supranuclear palsy (presynaptic PS). Drug-induced parkinsonism, a common, underdiagnosed health problem and psychogenic parkinsonism are causes of Parkinson's syndrome which, evidence suggests, occurs without degeneration of nigrostriatal structures. We review clinical features and results of DAT imaging in drug-induced parkinsonism and psychogenic parkinsonism. These two conditions normally give normal striatal DAT imaging results; an abnormal result in either case could exclude both conditions, corroborating a diagnosis of organic parkinsonism in uncertain cases. PMID:14531043

  2. Drug-induced Parkinsonism versus Idiopathic Parkinson Disease: Utility of Nigrosome 1 with 3-T Imaging.

    PubMed

    Sung, Young Hee; Noh, Young; Lee, Jongho; Kim, Eung Yeop

    2016-06-01

    Purpose To explore the utility of nigrosome 1 with 3-T magnetic resonance (MR) imaging to differentiate idiopathic Parkinson disease (IPD) from drug-induced parkinsonism (DIP). Materials and Methods The institutional review board approved this study, and participants gave informed consent. This study enrolled patients with DIP (n = 20) and IPD (n = 29) who underwent N-3-fluoropropyl-2-β-carbomethoxy-3-β-(4-iodophenyl)nortropane ((18)F-FP-CIT) positron emission tomography (PET) and healthy participants (n = 20). All participants underwent 0.5 × 0.5 × 1.0 mm(3) oblique axial three-dimensional multiecho-data image combination imaging to view the nigrosome 1 with 3-T imaging. Two reviewers independently assessed the nigrosome 1 without clinical information. DIP was diagnosed when no abnormality was seen at (18)F-FP-CIT PET. Diagnostic sensitivity, specificity, and accuracy of the nigrosome 1 imaging were evaluated between the IPD and DIP patients and between the IPD patients and healthy participants. Interrater agreement was assessed with Cohen κ. Results Both reviewers agreed in 63 of 69 participants (91.3%) for the presence of any abnormality on either side of the nigrosome 1 (κ = 0.825). Findings in all 29 IPD patients (100%) and three of 20 DIP patients (15%) were rated as abnormal and in 17 of 20 DIP patients (85%) they were interpreted as normal on the basis of imaging of the nitgrosome 1 (sensitivity, 100% (29 of 29); specificity, 85.0% (17 of 20); accuracy, 93.9% (46 of 49) between IPD and DIP patients). Findings in 3 of 20 healthy participants (15.0%) were interpreted as abnormal on the basis of imaging the nigrosome 1 while in the other 17 of 20 healthy participants (85.0%) they were rated as normal (sensitivity, 100% [29 of 29]; specificity, 85.0% [17 of 20]; accuracy, 93.9% [46 of 49] between IPD patients and healthy participants [κ = 0.831]). Conclusion The imaging of nigrosome 1 with 3-T imaging can differentiate DIP from IPD with high accuracy and

  3. Quantitative measurement of handwriting in the assessment of drug-induced parkinsonism.

    PubMed

    Caligiuri, Michael P; Teulings, Hans-Leo; Filoteo, J Vincent; Song, David; Lohr, James B

    2006-10-01

    Monitoring drug-induced side effects is especially important for patients who undergo treatment with antipsychotic medications, as these drugs often produce extrapyramidal side effects (EPS) resulting in movement abnormalities similar to parkinsonism. Scientists have developed several objective laboratory tests to measure and research drug-induced movement disorders, but equipment and tests are complex and costly and have not become accepted in large-scale, multi-site clinical trials. The goals of this study were to test whether a simple handwriting measure can discriminate between individuals with psychotropic-induced parkinsonism, Parkinson's disease, and healthy individuals, and to examine some of the psychometric properties of the measure. We examined pen movement kinematics during cursive writing of a standard word in 13 patients with idiopathic Parkinson's disease (PD), 10 schizophrenia patients with drug-induced parkinsonism (SZ), and 12 normal healthy control participants (NC). Participants were instructed to write the word "hello" in cursive twice, at three vertical height scales. Software was used for data acquisition and analysis of vertical stroke velocities, velocity scaling, and smoothness. There were four important results from this study: (1) both SZ patients with drug-induced EPS and PD participants exhibited impaired movement velocities and velocity scaling; (2) performance on the velocity scaling measure distinguished drug-induced EPS from normal with 90% accuracy; (3) SZ, but not PD participants displayed abnormalities in movement smoothness; and (4) there was a positive correlation between age and magnitude of the velocity scaling deficit in PD participants. This study demonstrates that kinematic analyses of pen movements during handwriting may be useful in detecting and monitoring subtle changes in motor control related to the adverse effects of psychotropic medications. PMID:16647772

  4. Persistent Drug-Induced Parkinsonism in Patients with Normal Dopamine Transporter Imaging

    PubMed Central

    Sunwoo, Mun Kyung; Oh, Jungsu S.; Kim, Jae Seung; Sohn, Young H.; Lee, Phil Hyu

    2016-01-01

    Functional neuroimaging for the dopamine transporter (DAT) is used to distinguish drug-induced parkinsonism (DIP) from subclinical Parkinson’s disease (PD). Although DIP patients who show a normal DAT image are expected to recover completely, some do not. We investigated whether these patients showed changes in striatal DAT activity using semi-quantitative analysis of 18F-FP-CIT PET data. DIP patients with visually normal DAT images were selected from medical records. The subjects were classified as patients who recovered partially (PR) or completely within 12 months (CR). The 18F-FP-CIT uptake in each striatal subregion was compared between the CR and the PR groups. In total, 41 and 9 patients of the CR and PR groups were assessed, respectively. The two patient groups were comparable in terms of clinical characteristics including age, sex, and severity of parkinsonism. From semi-quantitative analysis of the PET image, the PR patients showed a relatively lower ligand uptake in the ventral striatum, the anterior putamen and the posterior putamen compared with the CR patients. This result suggests that persistent DIP in patients with visually normal DAT imaging may be associated with subtle decrement of DAT activity. PMID:27294367

  5. The diagnosis of manganese-induced parkinsonism.

    PubMed

    Cersosimo, Maria G; Koller, William C

    2006-05-01

    Parkinsonism is a clinical syndrome consisting of tremor, bradykinesia, rigidity, gait, balance problems, in addition to various non-motor symptoms. There are many causes of parkinsonism such as neurodegenerative disease, drugs, vascular causes, structural lesions, infections, and toxicants. Parkinson's disease, or idiopathic parkinsonism, is the most common form of parkinsonism observed in the clinic. There is degeneration of the substantia nigra, pars compacta, which results in loss of striatal dopamine. Parkinson's disease is a slowly progressive condition in which there is a dramatic and sustained responsiveness to levodopa therapy. Manganese is an essential trace element that can be associated with neurotoxicity. Hypermanganism can occur in a variety of clinical settings. The clinical symptoms of manganese intoxication include non-specific complaints, neurobehavioral changes, parkinsonism, and dystonia. Although the globus pallidus is the main structure of damage, other basal ganglia areas can also be involved. MRI scans may show globus pallidus changes during (and for a short period after) exposure. Fluorodopa PET scans that assess the integrity of the substantia nigra dopaminergic system are abnormal in Parkinson's disease. However, these scans re-reported to be normal in a few cases studied with manganese-induced parkinsonism. The parkinsonism due to manganese may have some clinical features that occur less commonly in Parkinson's disease, such as kinetic tremor, dystonia, specific gait disturbances, and early mental, balance and speech changes. The clinical signs tend to be bilateral whereas Parkinson's disease begins on one side of the body. Patients with manganese-induced parkinsonism may be younger at the onset of the disease than with Parkinson's disease. Lastly, there appears to be a lack of response to levodopa therapy in manganese-induced parkinsonism. In summary it may be possible to differentiate manganese-induced parkinsonism from Parkinson

  6. Use of Fall-Risk Inducing Drugs in Patients Using Anti-Parkinson Drugs (APD): A Swedish Register-Based Study

    PubMed Central

    Haasum, Ylva; Fastbom, Johan; Johnell, Kristina

    2016-01-01

    Objectives Many drugs increase the risk of falls in old age. Although persons with Parkinson’s disease (PD) are at increased risk of experiencing falls and fractures, the use of fall-risk inducing drugs (FRIDs) in this population has not previously been investigated. The objective of this study was to investigate the burden of use of FRIDs in older persons treated with anti-Parkinson drugs (APD; used as a proxy for PD), compared to persons without APD. Methods We analyzed individual data on age, sex, type of housing and drug use in 1 346 709 persons aged ≥ 65 years in the Swedish Prescribed Drug Register on the date of 30 September 2008. Main outcome measure was the use of FRIDs. Results FRIDs were used by 79% of persons with APD and 75% of persons without APD. Persons with APD were more likely to use ≥ 1 FRIDs compared to persons without APD (adjusted OR: 1.09; 95% CI: 1.06-1-12). The association was stronger for concomitant use of ≥ 5 FRIDS (adjusted OR: 1.49; 95% CI: 1.44–1.55). Conclusions The high use of FRIDs among persons with APD indicates that these patients may be at increased risk of drug-induced falls. Further studies are needed to investigate how these drugs affect the risk of falling in persons with PD. PMID:27537366

  7. Drugs of abuse and Parkinson's disease.

    PubMed

    Mursaleen, Leah R; Stamford, Jonathan A

    2016-01-01

    The term "drug of abuse" is highly contextual. What constitutes a drug of abuse for one population of patients does not for another. It is therefore important to examine the needs of the patient population to properly assess the status of drugs of abuse. The focus of this article is on the bidirectional relationship between patients and drug abuse. In this paper we will introduce the dopaminergic systems of the brain in Parkinson's and the influence of antiparkinsonian drugs upon them before discussing this synergy of condition and medication as fertile ground for drug abuse. We will then examine the relationship between drugs of abuse and Parkinson's, both beneficial and deleterious. In summary we will draw the different strands together and speculate on the future merit of current drugs of abuse as treatments for Parkinson's disease. PMID:25816790

  8. Drug-induced parkinsonism: cinnarizine and flunarizine are potent uncouplers of the vacuolar H+-ATPase in catecholamine storage vesicles.

    PubMed

    Terland, O; Flatmark, T

    1999-06-01

    Cinnarizine (1-diphenylmethyl-4-(3-phenyl-2-propenyl)piperazine) and its di-fluorinated derivative flunarizine inhibit the MgATP-dependent generation of a transmembrane proton electrochemical gradient in chromaffin granule ghosts. The concentrations giving 50% inhibition (IC50) of the MgATP-dependent generation of the pH-gradient were 5.9+/-0.6 microM (n = 6) and 3.0+/-0.3 microM (n = 5) for cinnarizine and flunarizine, respectively. The IC50 values for inhibiting the generation of the membrane potential were even lower, i.e. 0.19+/-0.06 microM (n = 6) and 0.15+/-0.01 microM (n = 4) for cinnarizine and flunarizine, respectively. Cinnarizine (10 microM) also inhibited the energy-dependent vesicular uptake of [14C]-dopamine (50 microM) by 76%, i.e. from 2.1+/-0.9 to 0.5+/-0.6 nmol/mg protein/min (n = 5, P < 0.002). Cinnarizine (10 microM) increased the MgATPase activity of the granule ghosts by 47+/-26% (n = 4) compatible with an uncoupling of the vacuolar H+-ATPase activity. The IC50-values observed for the two compounds are in the same range as their reported therapeutic plasma concentrations in vivo, suggesting that cinnarizine and flunarizine may well inhibit proton pumping and catecholamine uptake in storage vesicles also in vivo. This mechanism of action may contribute to the drug-induced parkinsonism seen as a side-effect of the two drugs. PMID:10465691

  9. [The new Parkinson's disease drugs].

    PubMed

    Hasegawa, K

    2000-10-01

    The purpose of the new drugs for Parkinson's disease is control of the long-term levodopa treatment syndromes, especially wearing-off phenomenon and dyskinesia. Therefore, they show long T1/2. Most of them are classified into dopamine agonists. Others are monoamine oxidase B inhibitor and cathecole-o-methyltransferase inhibitor. Marketed dopamine agonists are bromocriptine, pergolide, talipexole, and cabergoline in Japan. Except talipexole, they are all ergot alkaloid derivatives. Their affinity for dopamine receptor is D2 group, and their T1/2 are longer than levodopa. Bromocriptine is an oldest dopamine agonist. Other 3 drugs and bromocriptine had made each other double blinded cross over trial previously. The result of double blinded studies show that their efficacy for PD treatment were equal, 40-50% patients with PD. However, in clinical usage, some difference is observed as described below. Efficacy of pergolide is strong compared with bromocriptine; however, pergolide is easy to arise dyskinesia. Talipexole is strong in the hypnosis effect. As for cabergoline, it takes long time to show medical effect, so that it is expected to control wearing-off phenomenon. Monoamine oxidase B inhibitor, Selegiline, is useful as an economizer effect to levodopa. As for the cathechole-o-methyltransferase inhibitor (COMT-I) will be make double-blinded trial in future. The efficacy for PD treatment of COMT-I is prolonged levodopa effect for PD, so that wearing-off phenomenon will be controlled. To use these drugs successfully is important with the treatment of PD. In the future, the development of the cause therapy in addition to the systematic therapy is wanted. PMID:11068448

  10. Drug induced parkinsonism caused by the concurrent use of donepezil and risperidone in a patient with traumatic brain injuries.

    PubMed

    Kang, Si Hyun; Kim, Don-Kyu

    2013-02-01

    A 69-year-old male patient with previous history of traumatic brain injury 5 months ago was admitted to the Department of Neuropsychiatry because of aggressive behavior and delusional features. After starting on 2 mg of risperidone per day, his delusion, anxiety, and aggressive behavior gradually improved. Two weeks later, he was given 10 mg of donepezil per day for his mild cognitive impairment. After 6 weeks of admission in the Department of Neuropsychiatry, he showed parkinsonian features including difficulty in walking, decreased arm swing during walking, narrowed step width, scooped posture, bradykinesia, tremor, and sleep disorder. To rule out the primary Parkinsonism, dopamine transporter imaging technique [18F]fluoropropyl-carbomethoxy-iodopropyl-nor-β-tropane positron emission tomography-computed tomography (18F]FP(IT PET-CT)) was performed, and dopamine transporter activity was not decreased. We considered that his parkinsonian features were associated with the combination of risperidone and donepezil. Both drugs were stopped and symptoms rapidly disappeared in several days. PMID:23526695

  11. Freezing of Gait in Parkinsonism and its Potential Drug Treatment.

    PubMed

    Zhang, Li-Li; Canning, S Duff; Wang, Xiao-Ping

    2016-01-01

    Freezing of gait (FOG) is a heterogeneous symptom. Studies of treatment for FOG are scarce. Levodopa and monoamine oxidase inhibitors (rasagiline and selegiline) have shown effective improvement for FOG. Other drugs, such as L-threo-3, 4-dihydroxyphenylserine, amantadine, and botulinum toxin have exhibited some beneficial effects. The present review summarizes the potential drug treatment for FOG in Parkinsonism. PMID:26635194

  12. Antipsychotic Drugs Tied to Risk of Early Death in Parkinson's Patients

    MedlinePlus

    ... Drugs Tied to Risk of Early Death in Parkinson's Patients But it's unclear whether the medications or ... 22, 2016 (HealthDay News) -- New research suggests that Parkinson's patients who are given antipsychotics to treat dementia ...

  13. Eye Movements in Ephedrone-Induced Parkinsonism

    PubMed Central

    Megrelishvili, Marika; Sieger, Tomáš; Matoušková, Olga; Okujava, Michael; Brožová, Hana; Nikolai, Tomáš; Hanuška, Jaromír; Kapianidze, Mariam; Mikeladze, Nina; Botchorishvili, Nazi; Khatiashvili, Irine; Janelidze, Marina; Serranová, Tereza; Fiala, Ondřej; Roth, Jan; Bergquist, Jonas; Jech, Robert; Rivaud-Péchoux, Sophie; Gaymard, Bertrand; Růžička, Evžen

    2014-01-01

    Patients with ephedrone parkinsonism (EP) show a complex, rapidly progressive, irreversible, and levodopa non-responsive parkinsonian and dystonic syndrome due to manganese intoxication. Eye movements may help to differentiate parkinsonian syndromes providing insights into which brain networks are affected in the underlying disease, but they have never been systematically studied in EP. Horizontal and vertical eye movements were recorded in 28 EP and compared to 21 Parkinson's disease (PD) patients, and 27 age- and gender-matched healthy subjects using standardized oculomotor tasks with infrared videooculography. EP patients showed slow and hypometric horizontal saccades, an increased occurrence of square wave jerks, long latencies of vertical antisaccades, a high error rate in the horizontal antisaccade task, and made more errors than controls when pro- and antisaccades were mixed. Based on oculomotor performance, a direct differentiation between EP and PD was possible only by the velocity of horizontal saccades. All remaining metrics were similar between both patient groups. EP patients present extensive oculomotor disturbances probably due to manganese-induced damage to the basal ganglia, reflecting their role in oculomotor system. PMID:25117825

  14. Manganese-Induced Parkinsonism and Parkinson's Disease: Shared and Distinguishable Features.

    PubMed

    Kwakye, Gunnar F; Paoliello, Monica M B; Mukhopadhyay, Somshuvra; Bowman, Aaron B; Aschner, Michael

    2015-07-01

    Manganese (Mn) is an essential trace element necessary for physiological processes that support development, growth and neuronal function. Secondary to elevated exposure or decreased excretion, Mn accumulates in the basal ganglia region of the brain and may cause a parkinsonian-like syndrome, referred to as manganism. The present review discusses the advances made in understanding the essentiality and neurotoxicity of Mn. We review occupational Mn-induced parkinsonism and the dynamic modes of Mn transport in biological systems, as well as the detection and pharmacokinetic modeling of Mn trafficking. In addition, we review some of the shared similarities, pathologic and clinical distinctions between Mn-induced parkinsonism and Parkinson's disease. Where possible, we review the influence of Mn toxicity on dopamine, gamma aminobutyric acid (GABA), and glutamate neurotransmitter levels and function. We conclude with a survey of the preventive and treatment strategies for manganism and idiopathic Parkinson's disease (PD). PMID:26154659

  15. Anchanling reduces pathology in a lactacystin- induced Parkinson's disease model☆

    PubMed Central

    Li, Yinghong; Wu, Zhengzhi; Gao, Xiaowei; Zhu, Qingwei; Jin, Yu; Wu, Anmin; Huang, Andrew C. J.

    2012-01-01

    A rat model of Parkinson's disease was induced by injecting lactacystin stereotaxically into the left mesencephalic ventral tegmental area and substantia nigra pars compacta. After rats were intragastrically perfused with Anchanling, a Chinese medicine, mainly composed of magnolol, for 5 weeks, when compared with Parkinson's disease model rats, tyrosine hydroxylase expression was increased, α-synuclein and ubiquitin expression was decreased, substantia nigra cell apoptosis was reduced, and apomorphine-induced rotational behavior was improved. Results suggested that Anchanling can ameliorate Parkinson's disease pathology possibly by enhancing degradation activity of the ubiquitin-proteasome system. PMID:25767493

  16. Manganese-Induced Parkinsonism Is Not Idiopathic Parkinson’s Disease: Environmental and Genetic Evidence

    PubMed Central

    Guilarte, Tomás R.; Gonzales, Kalynda K.

    2015-01-01

    Movement abnormalities caused by chronic manganese (Mn) intoxication clinically resemble but are not identical to those in idiopathic Parkinson’s disease. In fact, the most successful parkinsonian drug treatment, the dopamine precursor levodopa, is ineffective in alleviating Mn-induced motor symptoms, implying that parkinsonism in Mn-exposed individuals may not be linked to midbrain dopaminergic neuron cell loss. Over the last decade, supporting evidence from human and nonhuman primates has emerged that Mn-induced parkinsonism partially results from damage to basal ganglia nuclei of the striatal “direct pathway” (ie, the caudate/putamen, internal globus pallidus, and substantia nigra pars reticulata) and a marked inhibition of striatal dopamine release in the absence of nigrostriatal dopamine terminal degeneration. Recent neuroimaging studies have revealed similar findings in a particular group of young drug users intravenously injecting the Mn-containing psychostimulant ephedron and in individuals with inherited mutations of the Mn transporter gene SLC30A10. This review will provide a detailed discussion about the aforementioned studies, followed by a comparison with their rodent analogs and idiopathic parkinsonism. Together, these findings in combination with a limited knowledge about the underlying neuropathology of Mn-induced parkinsonism strongly support the need for a more complete understanding of the neurotoxic effects of Mn on basal ganglia function to uncover the appropriate cellular and molecular therapeutic targets for this disorder. PMID:26220508

  17. Drug-induced hepatitis

    MedlinePlus

    Toxic hepatitis ... to get liver damage. Some drugs can cause hepatitis with small doses, even if the liver breakdown ... liver. Many different drugs can cause drug-induced hepatitis. Painkillers and fever reducers that contain acetaminophen are ...

  18. Drug-induced hypoglycemia

    MedlinePlus

    ... medlineplus.gov/ency/article/000310.htm Drug-induced hypoglycemia To use the sharing features on this page, please enable JavaScript. Drug-induced hypoglycemia is low blood sugar that results from medication. ...

  19. A Case of SSRI Induced Irreversible Parkinsonism

    PubMed Central

    Khan, Shahbaj A; Azad, Sudip

    2015-01-01

    Serotonin specific reuptake inhibitors (SSRI) are widely used antidepressants for variety of clinical conditions and have found popularity. They are sometimes associated with extrapyramidal side effects including Parkinsonism. We report a case of generalized anxiety disorder on treatment with SSRI (fluoxetine / sertraline) who developed irreversible Parkinsonism. SSRI are known to cause reversible or irreversible motor disturbances through pathophysiological changes in basal ganglion motor system by altering the dopamine receptors postsynaptically. Clinician should keep risk benefit ratio in mind and change of antidepressant of different class may be considered. Case is reported to alert physicians to possibility of motor system damage while treating with SSRI. PMID:25859504

  20. Republished: drug-induced valvular heart disease.

    PubMed

    Cosyns, Bernard; Droogmans, Steven; Rosenhek, Raphael; Lancellotti, Patrizio

    2013-03-01

    Drug-induced valvular heart disease (DIVHD) was first described in the 1960s. Initially, associations with ergot derivatives used for migraine prevention, or with anorectic drugs, were described. Drugs used for the treatment of Parkinson's disease and endocrine diseases, like hyperprolactinemia, may also induce VHD. More recently, the use of 3,4-methylendioxymetamphetamine (MDMA, 'Ecstasy') and benfluorexhave been found to be associated with DIVHD. Although some of these drugs were withdrawn from the market, several cases of patients requiring valve surgery even years after the cessation of therapy have been reported. DIVHD is not infrequent, may be severe, and has been described in association with several drugs. Even after drug cessation, long-term implications of this type of VHD may persist. The present review underlines the need for a careful evaluation of the associated clinical and echocardiographic risk factors to allow early recognition so as not to delay appropriate management. PMID:23417686

  1. Drug-induced valvular heart disease.

    PubMed

    Cosyns, Bernard; Droogmans, Steven; Rosenhek, Raphael; Lancellotti, Patrizio

    2013-01-01

    Drug-induced valvular heart disease (DIVHD) was first described in the 1960s. Initially, associations with ergot derivatives used for migraine prevention, or with anorectic drugs, were described. Drugs used for the treatment of Parkinson's disease and endocrine diseases, like hyperprolactinemia, may also induce VHD. More recently, the use of 3,4-methylendioxymetamphetamine (MDMA, 'Ecstasy') and benfluorexhave been found to be associated with DIVHD. Although some of these drugs were withdrawn from the market, several cases of patients requiring valve surgery even years after the cessation of therapy have been reported. DIVHD is not infrequent, may be severe, and has been described in association with several drugs. Even after drug cessation, long-term implications of this type of VHD may persist. The present review underlines the need for a careful evaluation of the associated clinical and echocardiographic risk factors to allow early recognition so as not to delay appropriate management. PMID:22875739

  2. Exosomes as drug delivery vehicles for Parkinson's disease therapy.

    PubMed

    Haney, Matthew J; Klyachko, Natalia L; Zhao, Yuling; Gupta, Richa; Plotnikova, Evgeniya G; He, Zhijian; Patel, Tejash; Piroyan, Aleksandr; Sokolsky, Marina; Kabanov, Alexander V; Batrakova, Elena V

    2015-06-10

    Exosomes are naturally occurring nanosized vesicles that have attracted considerable attention as drug delivery vehicles in the past few years. Exosomes are comprised of natural lipid bilayers with the abundance of adhesive proteins that readily interact with cellular membranes. We posit that exosomes secreted by monocytes and macrophages can provide an unprecedented opportunity to avoid entrapment in mononuclear phagocytes (as a part of the host immune system), and at the same time enhance delivery of incorporated drugs to target cells ultimately increasing drug therapeutic efficacy. In light of this, we developed a new exosomal-based delivery system for a potent antioxidant, catalase, to treat Parkinson's disease (PD). Catalase was loaded into exosomes ex vivo using different methods: the incubation at room temperature, permeabilization with saponin, freeze-thaw cycles, sonication, or extrusion. The size of the obtained catalase-loaded exosomes (exoCAT) was in the range of 100-200nm. A reformation of exosomes upon sonication and extrusion, or permeabilization with saponin resulted in high loading efficiency, sustained release, and catalase preservation against proteases degradation. Exosomes were readily taken up by neuronal cells in vitro. A considerable amount of exosomes was detected in PD mouse brain following intranasal administration. ExoCAT provided significant neuroprotective effects in in vitro and in vivo models of PD. Overall, exosome-based catalase formulations have a potential to be a versatile strategy to treat inflammatory and neurodegenerative disorders. PMID:25836593

  3. Thrombocytopenia - drug induced

    MedlinePlus

    ... and a seizure medicine called valproic acid may lead to this problem. Other medicines that cause drug-induced thrombocytopenia include: Furosemide Gold, used to treat arthritis Nonsteroidal anti-inflammatory drugs ( ...

  4. Drug-induced nightmares.

    PubMed

    2000-12-01

    (1) A wide variety of drugs have been implicated in nightmares, often on inadequate evidence. (2) Recurrent nightmares can be induced by many drugs, and not only agents with psychotropic or neurological effects. PMID:11475499

  5. α6β2* and α4β2* Nicotinic Acetylcholine Receptors As Drug Targets for Parkinson's Disease

    PubMed Central

    Wonnacott, Susan

    2011-01-01

    Parkinson's disease is a debilitating movement disorder characterized by a generalized dysfunction of the nervous system, with a particularly prominent decline in the nigrostriatal dopaminergic pathway. Although there is currently no cure, drugs targeting the dopaminergic system provide major symptomatic relief. As well, agents directed to other neurotransmitter systems are of therapeutic benefit. Such drugs may act by directly improving functional deficits in these other systems, or they may restore aberrant motor activity that arises as a result of a dopaminergic imbalance. Recent research attention has focused on a role for drugs targeting the nicotinic cholinergic systems. The rationale for such work stems from basic research findings that there is an extensive overlap in the organization and function of the nicotinic cholinergic and dopaminergic systems in the basal ganglia. In addition, nicotinic acetylcholine receptor (nAChR) drugs could have clinical potential for Parkinson's disease. Evidence for this proposition stems from studies with experimental animal models showing that nicotine protects against neurotoxin-induced nigrostriatal damage and improves motor complications associated with l-DOPA, the “gold standard” for Parkinson's disease treatment. Nicotine interacts with multiple central nervous system receptors to generate therapeutic responses but also produces side effects. It is important therefore to identify the nAChR subtypes most beneficial for treating Parkinson's disease. Here we review nAChRs with particular emphasis on the subtypes that contribute to basal ganglia function. Accumulating evidence suggests that drugs targeting α6β2* and α4β2* nAChR may prove useful in the management of Parkinson's disease. PMID:21969327

  6. Therapies for dopaminergic-induced dyskinesias in Parkinson disease.

    PubMed

    Gottwald, Mildred D; Aminoff, Michael J

    2011-06-01

    Existing and emerging strategies for managing L-dopa-induced dyskinesias (LIDs) in patients with Parkinson disease have involved either delaying the introduction of L-dopa therapy, treatment with an antidyskinetic agent, using a therapy or delivery system that can provide continuous dopaminergic stimulation, or using novel agents that target receptors implicated in the mechanisms underlying LIDs. Treatment with dopamine agonists such as pramipexole or ropinirole allows levodopa to be delayed, but once levodopa is added to the drug regimen the usual course of onset of dyskinesias is observed. Amantadine, an N-methyl-D-aspartate antagonist, is so far the only approved compound with evidence of providing a sustained antidyskinetic benefit in the absence of unacceptable side effects. These findings support the hypothesis of glutamate overactivity in the development of dyskinesias. More continuous delivery of dopaminergic medication, such as through intraintestinal or subcutaneous routes, is promising but invasive and associated with injection site reactions. As a result of molecular research and elucidation of the role of a variety of neurotransmitters in the mechanism of LIDs, new compounds have been identified, including those that modulate the direct and indirect striatal output pathways; some of these new agents are in the early stages of development or undergoing proof-of-concept evaluation as antidyskinetic agents. PMID:21681795

  7. Aminochrome induces dopaminergic neuronal dysfunction: a new animal model for Parkinson's disease.

    PubMed

    Herrera, Andrea; Muñoz, Patricia; Paris, Irmgard; Díaz-Veliz, Gabriela; Mora, Sergio; Inzunza, Jose; Hultenby, Kjell; Cardenas, Cesar; Jaña, Fabián; Raisman-Vozari, Rita; Gysling, Katia; Abarca, Jorge; Steinbusch, Harry W M; Segura-Aguilar, Juan

    2016-09-01

    L-Dopa continues to be the gold drug in Parkinson's disease (PD) treatment from 1967. The failure to translate successful results from preclinical to clinical studies can be explained by the use of preclinical models which do not reflect what happens in the disease since these induce a rapid and extensive degeneration; for example, MPTP induces a severe Parkinsonism in only 3 days in humans contrasting with the slow degeneration and progression of PD. This study presents a new anatomy and develops preclinical model based on aminochrome which induces a slow and progressive dysfunction of dopaminergic neurons. The unilateral injection of aminochrome into rat striatum resulted in (1) contralateral rotation when the animals are stimulated with apomorphine; (2) absence of significant loss of tyrosine hydroxylase-positive neuronal elements both in substantia nigra and striatum; (3) cell shrinkage; (4) significant reduction of dopamine release; (5) significant increase in GABA release; (6) significant decrease in the number of monoaminergic presynaptic vesicles; (7) significant increase of dopamine concentration inside of monoaminergic vesicles; (8) significant increase of damaged mitochondria; (9) significant decrease of ATP level in the striatum (10) significant decrease in basal and maximal mitochondrial respiration. These results suggest that aminochrome induces dysfunction of dopaminergic neurons where the contralateral behavior can be explained by aminochrome-induced ATP decrease required both for anterograde transport of synaptic vesicles and dopamine release. Aminochrome could be implemented as a new model neurotoxin to study Parkinson's disease. PMID:27001668

  8. Drug-induced panniculitides.

    PubMed

    Borroni, G; Torti, S; D'Ospina, R M; Pezzini, C

    2014-04-01

    A substantial number of all panniculitides fails to recognize a specific etiology, and that is true also for a relatively frequent type of panniculitis, such as erythema nodosum (EN). Between the recognized causative factors of panniculitides, infectious, physical agents, autoimmune mechanisms and neoplastic disorders are well known. On the contrary, the role of drugs as inducers of panniculitides is marginally considered, and their report limited to anecdotal observations, often without due histopathological support. Since the clinical and histopathological features of drug-induced panniculitides are indistinguishable from those caused by other agents, the causative relationship may be demonstrated by the history of previous drug intake and by clinical improvement after drug discontinuation. We reviewed the currently reported descriptions of drug-induced panniculitis, including a few exemplificative original observations. EN results as the most frequently reported drug-induced panniculitis. Among the causative drugs of EN a variety of medications, with disparate, or even opposite, mechanisms of action are reported, thus limiting the understanding of the pathogenesis. Common causative drugs include oral contraceptives, nonsteroidal anti-inflammatory drugs, antiobiotics and leukotriene-modifying agents. Unfortunately, in several cases, the diagnosis of drug-induced EN is done on clinical findings alone. In those cases, the lack of histopathological support does not allow to define a precise clinicopathological correlation on etiologic grounds. Drug-induced lobular and mixed panniculitides, including eosinophilic panniculitis, are even more rarely described. Reported causative agents are glatiramer acetate, interferon beta and heparin (at sites of injections), and systemic steroids, tyrosine kinase inhibitors and BRAF with subcutaneous fat involvement at distance. In view of the recent introduction of new classes of drugs, attention should be paid to disclose their

  9. Drug-induced hyperkalemia.

    PubMed

    Ben Salem, Chaker; Badreddine, Atef; Fathallah, Neila; Slim, Raoudha; Hmouda, Houssem

    2014-09-01

    Hyperkalemia is a common clinical condition that can be defined as a serum potassium concentration exceeding 5.0 mmol/L. Drug-induced hyperkalemia is the most important cause of increased potassium levels in everyday clinical practice. Drug-induced hyperkalemia may be asymptomatic. However, it may be dramatic and life threatening, posing diagnostic and management problems. A wide range of drugs can cause hyperkalemia by a variety of mechanisms. Drugs can interfere with potassium homoeostasis either by promoting transcellular potassium shift or by impairing renal potassium excretion. Drugs may also increase potassium supply. The reduction in renal potassium excretion due to inhibition of the renin-angiotensin-aldosterone system represents the most important mechanism by which drugs are known to cause hyperkalemia. Medications that alter transmembrane potassium movement include amino acids, beta-blockers, calcium channel blockers, suxamethonium, and mannitol. Drugs that impair renal potassium excretion are mainly represented by angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, direct renin inhibitors, nonsteroidal anti-inflammatory drugs, calcineurin inhibitors, heparin and derivatives, aldosterone antagonists, potassium-sparing diuretics, trimethoprim, and pentamidine. Potassium-containing agents represent another group of medications causing hyperkalemia. Increased awareness of drugs that can induce hyperkalemia, and monitoring and prevention are key elements for reducing the number of hospital admissions, morbidity, and mortality related to drug-induced hyperkalemia. PMID:25047526

  10. Phytochemicals as future drugs for Parkinson's disease: a comprehensive review.

    PubMed

    Shahpiri, Zahra; Bahramsoltani, Roodabeh; Hosein Farzaei, Mohammad; Farzaei, Fatemeh; Rahimi, Roja

    2016-08-01

    Parkinson's disease (PD) is the second most common chronic neurodegenerative disease that affects motor skills and cognitive performance. The conventional therapeutic approaches for the management of PD are just able to alleviate symptoms. Exploring for achieving novel substances with therapeutic benefits in PD patients is the focus of a wide range of current investigations. The aim of the present study is to comprehensively review phytochemicals with protective or therapeutic activities in PD and focus on their neuropsychopharmacological mechanisms. Various subgroups of polyphenols (flavonoids, phenolic acids, stilbenes, and lignanes) and terpenes are the most abundant groups of phytochemicals with well-established antiparkinsonian effects. Other phytochemical categories, such as alkaloids, cinnamates, carbohydrates, amino acids, and fatty acid amides, also have some representatives with positive effects in PD. Phytochemicals perform their antiparkinsonian effect through several mechanisms of action, including suppressing apoptosis (via the reduction of Bax/Bcl-2, caspase-3, -8, and -9, and α-synuclein accumulation), decreasing dopaminergic neuronal loss and dopamine depletion, reducing the expression of proinflammatory cytokines (such as prostaglandin E2, interleukin-6, interleukin-1β, and nuclear factor-κB), and modulating nuclear and cellular inflammatory signaling, elevation of neurotrophic factors, and improvement of antioxidant status. Plant-derived natural products can be considered as future pharmaceutical drugs or adjuvant treatment with conventional therapeutic approaches to improve their efficacy and alleviate their psychological adverse effects in the management of PD. Well-designed clinical trials are mandatory to evaluate the protective and healing benefits of phytochemicals as promising future drugs in the management of neurodegenerative diseases. PMID:27124673

  11. Vitiligo, drug induced (image)

    MedlinePlus

    ... this person's face have resulted from drug-induced vitiligo. Loss of melanin, the primary skin pigment, occasionally ... is the case with this individual. The typical vitiligo lesion is flat (macular) and depigmented, but maintains ...

  12. Vitiligo, drug induced (image)

    MedlinePlus

    ... drug-induced vitiligo. Loss of melanin, the primary skin pigment, occasionally occurs as a result of medications, as is the case with this individual. The typical vitiligo lesion is flat (macular) and depigmented, but maintains the normal skin texture.

  13. DRUG INDUCED CHOLESTASIS

    PubMed Central

    Padda, Manmeet S.; Sanchez, Mayra; Akhtar, Abbasi J.; Boyer, James L.

    2011-01-01

    Recent progress in understanding the molecular mechanisms of bile formation and cholestasis have led to new insights into the pathogenesis of drug induced cholestasis. This review summarizes their variable clinical presentations, examines the, role of transport proteins in hepatic drug clearance and toxicity and addresses the increasing importance of genetic determinants, as well as practical aspects of diagnosis and management. PMID:21480339

  14. [Parkinsonism, depression and akathisia induced by flunarizine, a calcium entry blockade--report of 31 cases].

    PubMed

    Kuzuhara, S; Kohara, N; Ohkawa, Y; Fuse, S; Yamanouchi, H

    1989-06-01

    Flunarizine hydrochloride (FZ), a calcium entry blockade, has been used nationwide in Japan as a cerebral active vasodilator since October, 1984. The present paper reports 31 cases of FZ-induced Parkinsonism, depression and akathisia, referred to our hospital between October 1986 and September 1988. Out of the 31 patients, four including two with Parkinson's disease and one each with progressive supranuclear palsy and olivopontocerebellar atrophy showed worsening of their parkinsonian symptoms within a few months after FZ administration. The remaining 27 patients (7 males and 20 females) newly developed Parkinsonism after treatment with FZ. Symptoms appeared one week to two years (mean: 6.1 months) after starting FZ of a daily dose of 10 mg. FZ had been used in 6 patients for cerebrovascular episodes confirmed by clinical history or brain CT, and in the remainder, for dizziness, light-headedness, hypertension, amnesia or hypochondric neurotic complaints. Akinesia and bradykinesia progressed rather rapidly after onset, and patients became unambulatory within several months. Symptoms had worsened, and L-dopa, anticholinergic drugs, and bromocriptine had been ineffective until FZ was discontinued. Their Parkinsonism was characterized by marked akinesia, bradykinesia, and moderate rigidity. Masked face was seen in most of them. Tremor was absent at rest, and induced in 12 patients by posture and/or action. Sixteen patients were accompanied by depression, and five, by akathisia. Improvement began several weeks after withdrawal of FZ, and most patients recovered almost completely within a few months although mild rigidity and bradykinesia remained in some.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2582681

  15. Drug-induced Photosensitivity.

    PubMed

    Zuba, Ewelina Bogumiła; Koronowska, Sandra; Osmola-Mańkowska, Agnieszka; Jenerowicz, Dorota

    2016-04-01

    Ultraviolet radiation is considered the main environmental physical hazard to the skin. It is responsible for photoaging, sunburns, carcinogenesis, and photodermatoses, including drug-induced photosensitivity. Drug-induced photosensitivity is an abnormal skin reaction either to sunlight or to artificial light. Drugs may be a cause of photoallergic, phototoxic, and photoaggravated dermatitis. There are numerous medications that can be implicated in these types of reactions. Recently, non-steroidal anti-inflammatory drugs have been shown to be a common cause of photosensitivity. As both systemic and topical medications may promote photosensitive reactions, it is important to take into consideration the potential risk of occurrence such reactions, especially in people chronically exposed to ultraviolet radiation. PMID:27149132

  16. Sodium salicylate protects against rotenone-induced parkinsonism in rats.

    PubMed

    Madathil, Sindhu K; Karuppagounder, Saravanan S; Mohanakumar, Kochupurackal P

    2013-08-01

    Complex I deficiency culminating in oxidative stress is proposed as one of the upstream mechanisms of nigral neuronal death in Parkinson's disease. We investigated whether sodium salicylate, an active metabolite of aspirin, could afford protection against rotenone-induced oxidative stress, neuronal degeneration, and behavioral dysfunction in rats, because it has the potential to accept a molecule each of hydroxyl radical (•OH) at the third or fifth position of its benzyl ring. Rotenone caused dose-dependent increase in •OH in isolated mitochondria from the cerebral cortex and time- (24-48 h) and dose-dependent (0.1-100 µM) increase in the substantia nigra and the striatum, ipsilateral to the side of rotenone infusion. Administration of sodium salicylate at 12-h intervals for 4 days showed dose-dependent (50-100 mg/kg, i.p) reductions in the levels of •OH in the nigra on the fifth day. These animals showed significant attenuation in rotenone-induced loss in striatal dopamine levels, number of nigral dopaminergic neurons, reduced and oxidized glutathione levels, and complex I activity loss, but superoxide dismutase activity was increased further. Amphetamine- or apomorphine-induced ipsilateral rotations in rotenone-treated rats were significantly reduced in rats treated with sodium salicylate. Our results indicate a direct role of •OH in mediating nigral neuronal death by rotenone and confirm the neuroprotective potential of salicylate in a rodent model of parkinsonism. PMID:23447126

  17. Tea and Parkinson's disease: Constituents of tea synergize with antiparkinsonian drugs to provide better therapeutic benefits.

    PubMed

    Dutta, Debashis; Mohanakumar, Kochupurackal P

    2015-10-01

    The major neurodegenerative movement disorder Parkinson's disease (PD) is characterized by rest-tremor, akinesia, rigidity and inability to initiate movements. PD syndromes result from excessive loss of dopamine from the forebrain striatal region, due to dopaminergic neuronal death in the midbrain substantia nigra pars compacta. PD with multifactorial etiology is believed to ideally require a drug or different drugs that act(s) at multiple sites of action for symptomatic relief. Replenishing striatal dopamine by providing L-3,4-dihydroxyphenylalanine (l-DOPA) along with a peripheral aromatic amino acid decarboxylase inhibitor is the mainstay treatment for PD. Such prolonged therapy leads to debilitating effects, often worsening the affection. Interestingly some under-appreciated pharmaceutical compounds, including constituents of plants and nutraceuticals can synergize with l-DOPA to support mitochondrial function, suppress inflammation, ease oxidative stress, and in turn slow the progression of the disease. Tea and other dietary polyphenols are shown to provide relief to the disease syndromes and provide neuroprotection in cellular and animal models of PD. At par with these findings, random epidemiological studies in certain populations of the world support habitual tea drinking to reduce the risk of PD. The present review addresses how these tea constituents work at the cellular level to render effective control of the disease syndromes and suggests that tea synergizes with established drugs, such as l-DOPA to maximize their effects at certain levels in the disease phenotype-inducing canonical pathways of PD. PMID:26271432

  18. Drug-induced tremor

    MedlinePlus

    ... stabilizers such as lithium carbonate Stimulants such as caffeine and amphetamines Selective serotonin reuptake inhibitors (SSRIs) Tricyclic ... Cigarette smoking Hyperthyroidism Parkinson disease Pheochromocytoma Too much caffeine Wilson disease Blood tests and imaging studies (such ...

  19. [Designer drug induced psychosis].

    PubMed

    Fullajtar, Mate; Ferencz, Csaba

    2012-06-01

    3,4-methylene-dioxy-pyrovalerone (MDPV) is a popular designer drug in Hungary, known as MP4. We present a case of a 34-year-old man, whose first psychotic episode was observed in the presence of MP4 use. The paranoid ideas of reference and the dereistic thinking could be the consequence of drug-induced psychosis. Within 24 hours after the intoxication was over delirium set in. The patient's history included only the use of MP4, use of other kinds of drugs was negated. The drug tests were negative, amphetamine derivates were not detectable in the urine sample. It is most likely that the MP4 pill contained an amount of MDPV less than detectable. In conclusion we suggest that the clinical picture could be the consequence of regular MDPV use. PMID:22710853

  20. Application of Several Multimedia Approaches to the Teaching of CNS Pharmacology: Parkinson's Disease and Antiparkinsonism Drugs.

    ERIC Educational Resources Information Center

    Faulkner, Thomas P.; Sprague, Jon E.

    1996-01-01

    A multimedia approach to drug therapy for Parkinson's Disease, part of a pharmacy school central nervous system course, integrated use of lecture, textbook, video/graphic technology, the movie "Awakenings," Internet and World Wide Web, and an interactive animated movie. A followup questionnaire found generally positive student attitudes toward the…

  1. Drug-Induced Hematologic Syndromes

    PubMed Central

    Mintzer, David M.; Billet, Shira N.; Chmielewski, Lauren

    2009-01-01

    Objective. Drugs can induce almost the entire spectrum of hematologic disorders, affecting white cells, red cells, platelets, and the coagulation system. This paper aims to emphasize the broad range of drug-induced hematological syndromes and to highlight some of the newer drugs and syndromes. Methods. Medline literature on drug-induced hematologic syndromes was reviewed. Most reports and reviews focus on individual drugs or cytopenias. Results. Drug-induced syndromes include hemolytic anemias, methemoglobinemia, red cell aplasia, sideroblastic anemia, megaloblastic anemia, polycythemia, aplastic anemia, leukocytosis, neutropenia, eosinophilia, immune thrombocytopenia, microangiopathic syndromes, hypercoagulability, hypoprothrombinemia, circulating anticoagulants, myelodysplasia, and acute leukemia. Some of the classic drugs known to cause hematologic abnormalities have been replaced by newer drugs, including biologics, accompanied by their own syndromes and unintended side effects. Conclusions. Drugs can induce toxicities spanning many hematologic syndromes, mediated by a variety of mechanisms. Physicians need to be alert to the potential for iatrogenic drug-induced hematologic complications. PMID:19960059

  2. Nobiletin treatment improves motor and cognitive deficits seen in MPTP-induced Parkinson model mice.

    PubMed

    Yabuki, Y; Ohizumi, Y; Yokosuka, A; Mimaki, Y; Fukunaga, K

    2014-02-14

    Nobiletin, a polymethoxylated flavonoid found in citrus fruit peel, reportedly improves memory impairment in rodent models. Here we report its effect on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced motor and cognitive deficits. Nobiletin administration (50mg/kg i.p.) for 2 consecutive weeks improved motor deficits seen in MPTP-induced Parkinson model mice by 2weeks, an effect that continued until 2weeks after drug withdrawal. Drug treatment promoted similar rescue of MPTP-induced cognitive impairment at equivalent time points. Nonetheless, nobiletin treatment did not block loss of dopaminergic neurons seen in the MPTP-treated mouse midbrain, nor did it rescue decreased tyrosine hydroxylase (TH) protein levels seen in the striatum or hippocampal CA1 region of these mice. Interestingly, nobiletin administration (50mg/kg i.p.) rescued reduced levels of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation and phosphorylation at Thr-34 of dopamine- and cAMP-regulated phosphoprotein-32 (DARPP-32) in striatum and hippocampal CA1 to levels seen in sham-operated mice. Likewise, CaMKII- and cAMP kinase-dependent TH phosphorylation was significantly restored by nobiletin treatment. MPTP-induced reduction of dopamine contents in the striatum and hippocampal CA1 region was improved by nobiletin administration (50mg/kg i.p.). Acute intraperitoneal administration of nobiletin also enhanced dopamine release in striatum and hippocampal CA1, an effect partially inhibited by treatment with nifedipine (a L-type Ca(2+) channel inhibitor) or NNC 55-0396 (a T-type Ca(2+) channel inhibitor) and completely abolished by combined treatment with both. Overall, our study describes a novel nobiletin activity in brain and suggests that nobiletin rescues motor and cognitive dysfunction in MPTP-induced Parkinson model mice, in part by enhancing dopamine release. PMID:24316474

  3. Manganese-induced Parkinsonism in a patient undergoing maintenance hemodialysis.

    PubMed

    Ohtake, Takayasu; Negishi, Kousuke; Okamoto, Kouji; Oka, Machiko; Maesato, Kyoko; Moriya, Hidekazu; Kobayashi, Shuzo

    2005-10-01

    We report a rare case of manganese (Mn)-induced parkinsonism in a patient on maintenance hemodialysis therapy who complained of gait disturbance and dysarthria. His symptoms and abnormal magnetic resonance imaging (MRI) findings of the brain were thought to be caused, at least in part, by long-term ingestion of a health supplement (Chlorella extract) that contained 1.7 mg of Mn in the usual daily dose. Elevated serum and cerebrospinal fluid Mn levels were detected, and brain MRI showed areas of abnormal intensity in the bilateral basal ganglia (low intensity on T1-weighted images and high intensity on T2-weighted images). Edetic acid infusion therapy dramatically improved the MRI abnormalities, after which his symptoms gradually improved 4 months later. PMID:16183431

  4. Neuroactive gonadal drugs for neuroprotection in male and female models of Parkinson's disease.

    PubMed

    Litim, Nadhir; Morissette, Marc; Di Paolo, Thérèse

    2016-08-01

    The existence of sex differences in Parkinson's disease (PD) incidence is well documented with greater prevalence and earlier age at onset in men than in women. These reported sex differences could be related to estrogen exposure. In PD animal models, estrogen is well documented to be neuroprotective against dopaminergic neuron loss induced by neurotoxins. Using the 1-methyl 4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) mouse model, we showed that several compounds are neuroprotective on dopaminergic neurons including estrogen, the selective estrogen receptor modulator raloxifene, progesterone, dehydroepiandrosterone, the estrogen receptor alpha (ERα) agonist PPT as well as the G protein-coupled membrane estrogen receptor (GPER1) specific agonist G1. Accumulating evidence suggests that GPER1 could be implicated in the neuroprotective effects of estrogen, raloxifene and G1 in collaboration with ERα. We recently reported that the 5α-reductase inhibitor Dutasteride is also neuroprotective and could bring an alternative to estrogens for therapy in male. Additional studies are needed to optimize therapies with these gonadal drugs into safe personalized treatments according to sex for treatment of PD. PMID:26708712

  5. Beneficial effect of antidepressants against rotenone induced Parkinsonism like symptoms in rats.

    PubMed

    Sharma, Nidhika; Jamwal, Sumit; Kumar, Puneet

    2016-06-01

    Parkinson's disease is a second most common age-related neurodegenerative disorder characterized by the loss of DA neurons of SNpc region of the midbrain. Neurotransmitter dysfunction is involved in the pathogenesis of PD. Antidepressants like venlafaxine and sertraline expected to improve Parkinsonism like symptoms by modulating the levels of various neurotransmitters. The neuroprotective role of antidepressants is well explored in various CNS disorders. Therefore, this study was designed to explore and compare the mechanistic role of different antidepressants (venlafaxine and sertraline) against rotenone induced Parkinsonism like symptoms in rats. Rats were administrated with rotenone (1.5mg/kg/day; s.c.) daily for a period of 28 days. Venlafaxine (10 and 20mg/kg; p.o.), sertraline (10 and 20mg/kg; p.o.) and Levodopa combination with Carbidopa (10mg/kg; p.o.) were administered daily starting from 7th day one hour prior to rotenone administration. Behavioral parameters (body weight, rotarod, grip strength, narrow beam walk and open field) were assessed on weekly basis. On 28th day, animals were sacrificed and striatum were isolated for biochemical (LPO, GSH and nitrite), neuroinflammatory (TNF-α, IL-1β and IL-6), neurochemical (DA, NE, 5-HT, GABA, Glutamate, DOPAC, HVA and 5-HIAA) and mitochondrial complex-I estimation. Rotenone administration significantly reduced body weight, motor coordination, oxidative defense, increased pro-inflammatory mediators and decreased level of catecholamines. Pre-treatment with venlafaxine and sertraline significantly attenuated the alteration in behavioral, oxidative stress, neuroinflammatory, mitochondrial and catecholamines level in striatum. The study provides a hope that these drugs could be used as adjuvant therapy in the management and treatment of PD. PMID:26996500

  6. [Drug-induced laryngospasm].

    PubMed

    Nishikawa, T; Munakata, K

    1997-02-01

    We report a case of drug-induced laryngospasm due to Chlorpromazine. A drug-induced laryngospasm has not been previously reported in the literature. A 70-year-old male with the proximal end fracture of the femur was scheduled for the operative fixation. He had a past history of alcoholism and had underwent a long-term chlorpromazine therapy for 45 years until admission to our hospital. There have been a few reports on unexplained sudden deaths of patients receiving long-term treatment with chlorpromazine. Caution was therefore needed in general anesthesia, which was thought to be safer than epidural or spinal anesthesia in this case. Accordingly for the preparation of an emergency operation, the central venous catheterization via the internal jugular vein was performed under subcutaneous injection of lidocaine. Severe dyspnea and cyanosis occurred a few minutes after the administration of lidocaine. The specific diagnosis of laryngospasm was made by inspection of the vocal cords. Immediate oral intubation was performed and no complications ensued during and after the operation. This episode strongly suggests that one reason of the unexplained sudden deaths of patients receiving long term treatment with chlorpromazine could be laryngospasm. In conclusion, anesthesiologists should be aware of the possibility of laryngospasm under similar conditions. PMID:9071116

  7. Meclizine-induced enhanced glycolysis is neuroprotective in Parkinson disease cell models

    PubMed Central

    Hong, Chien Tai; Chau, Kai-Yin; Schapira, Anthony H. V.

    2016-01-01

    Meclizine is a well-tolerated drug routinely used as an anti-histamine agent in the management of disequilibrium. Recently, meclizine has been assessed for its neuroprotective properties in ischemic stroke and Huntington disease models. We found that meclizine protected against 6-hydroxydopamine-induced apoptosis and cell death in both SH-SY5Y cells and rat primary cortical cultures. Meclizine increases the level of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), which activates phosphofructokinase, a rate-determining enzyme of glycolysis. This protection is therefore mediated by meclizine’s ability to enhance glycolysis and increase mitochondrial hyperpolarization. Meclizine represents an interesting candidate for further investigation to re-purpose for its potential to be neuroprotective in Parkinson disease. PMID:27145922

  8. Meclizine-induced enhanced glycolysis is neuroprotective in Parkinson disease cell models.

    PubMed

    Hong, Chien Tai; Chau, Kai-Yin; Schapira, Anthony H V

    2016-01-01

    Meclizine is a well-tolerated drug routinely used as an anti-histamine agent in the management of disequilibrium. Recently, meclizine has been assessed for its neuroprotective properties in ischemic stroke and Huntington disease models. We found that meclizine protected against 6-hydroxydopamine-induced apoptosis and cell death in both SH-SY5Y cells and rat primary cortical cultures. Meclizine increases the level of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), which activates phosphofructokinase, a rate-determining enzyme of glycolysis. This protection is therefore mediated by meclizine's ability to enhance glycolysis and increase mitochondrial hyperpolarization. Meclizine represents an interesting candidate for further investigation to re-purpose for its potential to be neuroprotective in Parkinson disease. PMID:27145922

  9. Drug-induced renal disorders.

    PubMed

    Ghane Shahrbaf, Fatemeh; Assadi, Farahnak

    2015-01-01

    Drug-induced nephrotoxicity are more common among infants and young children and in certain clinical situations such as underlying renal dysfunction and cardiovascular disease. Drugs can cause acute renal injury, intrarenal obstruction, interstitial nephritis, nephrotic syndrome, and acid-base and fluid electrolytes disorders. Certain drugs can cause alteration in intraglomerular hemodynamics, inflammatory changes in renal tubular cells, leading to acute kidney injury (AKI), tubulointerstitial disease and renal scarring. Drug-induced nephrotoxicity tends to occur more frequently in patients with intravascular volume depletion, diabetes, congestive heart failure, chronic kidney disease, and sepsis. Therefore, early detection of drugs adverse effects is important to prevent progression to end-stage renal disease. Preventive measures requires knowledge of mechanisms of drug-induced nephrotoxicity, understanding patients and drug-related risk factors coupled with therapeutic intervention by correcting risk factors, assessing baseline renal function before initiation of therapy, adjusting the drug dosage and avoiding use of nephrotoxic drug combinations. PMID:26468475

  10. Cancer Drug Shows Early Promise for Parkinson's Disease

    MedlinePlus

    ... that the drug boosted the brain's production of dopamine, a chemical that helps regulate movement. It also ... of certain brain cells -- including ones that produce dopamine, which help regulate movement. For the past 50 ...

  11. Neuroleptic-induced Parkinson's syndrome: clinical features and results of treatment with levodopa.

    PubMed Central

    Hardie, R J; Lees, A J

    1988-01-01

    Twenty six consecutive patients with neuroleptic-induced Parkinson's syndrome (NIPS) are described. Their median age was 61 years, 60% were female, and most had received chronic neuroleptic medication for psychiatric indications. The clinical features were indistinguishable from idiopathic Parkinson's disease, except for the presence of co-existing orofacial chorea, limb dyskinesia or akathisia which provided an aetiological clue in 11 cases. Complete resolution of NIPS occurred in only two patients, one of whom later developed Parkinson's disease. Sixteen patients were treated with 300-1000 mg levodopa/benserazide for up to 4 years with few adverse effects but therapeutic response was disappointing. PMID:2900293

  12. Drug-Induced Metabolic Acidosis.

    PubMed

    Pham, Amy Quynh Trang; Xu, Li Hao Richie; Moe, Orson W

    2015-01-01

    Metabolic acidosis could emerge from diseases disrupting acid-base equilibrium or from drugs that induce similar derangements. Occurrences are usually accompanied by comorbid conditions of drug-induced metabolic acidosis, and clinical outcomes may range from mild to fatal. It is imperative that clinicians not only are fully aware of the list of drugs that may lead to metabolic acidosis but also understand the underlying pathogenic mechanisms. In this review, we categorized drug-induced metabolic acidosis in terms of pathophysiological mechanisms, as well as individual drugs' characteristics. PMID:26918138

  13. Tetranectin gene deletion induces Parkinson's disease by enhancing neuronal apoptosis.

    PubMed

    Chen, Zhifeng; Wang, Ersong; Hu, Rong; Sun, Yu; Zhang, Lei; Jiang, Jue; Zhang, Ying; Jiang, Hong

    Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). We previously identified tetranectin (TET) as a potential biomarker for PD whose expression is downregulated in the cerebrospinal fluid of PD patients. In the present study, we investigate the role of TET in neurodegeneration in vitro and in vivo. Our results showed that siRNA knockdown of TET decreased cell viability and the number of tyrosine hydroxylase (TH) positive cells, whereas it increased caspase-3 activity and the Bax/Bcl-2 ratio in cultured primary dopaminergic neurons. Overexpression of TET protected dopaminergic neurons against neuronal apoptosis in 1-methyl-4-phenylpyridinium cell culture model in vitro. In TET knockdown mouse model of PD, TET gene deletion decreased the number of TH positive cells in the SNpc, induced apoptosis via the p53/Bax pathway, and significantly impaired the motor behavior of transgenic mice. The findings suggest that TET plays a neuroprotective role via reducing neuron apoptosis and could be a valuable biomarker or potential therapeutic target for the treatment of patients with PD. PMID:26597345

  14. Effect of centrophenoxine against rotenone-induced oxidative stress in an animal model of Parkinson's disease.

    PubMed

    Verma, Ranjeet; Nehru, Bimla

    2009-11-01

    Oxidative stress has been implicated in the etiology of Parkinson's disease (PD). The important biochemical features of PD, being profound deficit in dopamine (DA) content, reduced glutathione (GSH), and enhanced lipid peroxidation (LPO) in dopaminergic (DA-ergic) neurons resulting in oxidative stress, mitochondrial dysfunction and apoptosis. Rotenone-induced neurotoxicity is a well acknowledged preclinical model for studying PD in rodents as it produces selective DA-ergic neuronal degeneration. In our previous study, we have shown that chronic administration of rotenone to rats is able to produce motor dysfunction, which increases progressively with rotenone treatment and centrophenoxine (CPH) co-treatment is able to attenuate these motor defects. The present study was carried out to evaluate the antioxidant potential of CPH against rotenone-induced oxidative stress. Chronic administration of rotenone to SD rats resulted in marked oxidative damage in the midbrain region compared to other regions of the brain and CPH co-treatment successfully attenuated most of these changes. CPH significantly attenuated rotenone-induced depletion in DA, GSH and increase in LPO levels. In addition, the drug prevented the increase in nitric oxide (NO) and citrulline levels and also enhanced the activity of catalase and superoxide dismutase (SOD). Histological analysis carried out using hematoxylin and eosin staining has indicated severe damage to mid brain in comparison to cortex and cerebellum and this damage is attenuated by CPH co-treatment. Our results strongly indicate the possible therapeutic potential of centrophenoxine as an antioxidant in Parkinson's disease and other movement disorders where oxidative stress is a key player in the disease process. PMID:19375462

  15. Drug-Induced Itch Management.

    PubMed

    Ebata, Toshiya

    2016-01-01

    Drugs may cause itching as a concomitant symptom of drug-induced skin reactions or in the form of pruritus without skin lesions. Drug-induced itch is defined as generalized itching without skin lesions, caused by a drug. Itching associated with drug-induced cholestasis is among the common dermatologic adverse events (dAEs) that induce itching. Some drugs such as opioids, antimalarials, and hydroxyethyl starch are known to induce itching without skin lesions. The clinical features and underlying proposed mechanisms of itching caused by these drugs have been specifically investigated. The recent application of targeted anticancer drugs has increased the survival rate of cancer patients. These new agents cause significant dAEs such as acneiform rashes, dry skin, hand-foot syndrome, paronychia, and itching. Itching is a common side effect of epidermal growth factor receptor inhibitors. Though not life-threatening, these dAEs have a negative impact on a patient's quality of life, leading to dose reduction and possibly less effective cancer therapy. It is important to provide an effective supportive antipruritic treatment without interruption of the administration of these drugs. This chapter concludes by describing basic measures to be taken for diagnosis and treatment of drug-induced itch. The principle of treatment is discontinuation of suspected causative drugs in general except for anticancer medications. In case itching lasts long after drug withdrawal or the causative drug cannot be stopped, vigorous symptomatic antipruritic treatment and specific therapies for different types of drug-induced itch should be undertaken. PMID:27578085

  16. Drug-Induced Metabolic Acidosis

    PubMed Central

    Pham, Amy Quynh Trang; Xu, Li Hao Richie; Moe, Orson W.

    2015-01-01

    Metabolic acidosis could emerge from diseases disrupting acid-base equilibrium or from drugs that induce similar derangements. Occurrences are usually accompanied by comorbid conditions of drug-induced metabolic acidosis, and clinical outcomes may range from mild to fatal. It is imperative that clinicians not only are fully aware of the list of drugs that may lead to metabolic acidosis but also understand the underlying pathogenic mechanisms. In this review, we categorized drug-induced metabolic acidosis in terms of pathophysiological mechanisms, as well as individual drugs’ characteristics. PMID:26918138

  17. [Drug treatment of early-stage (de novo and "honeymoon") Parkinson disease].

    PubMed

    Cesaro, P; Defebvre, L

    2014-04-01

    In this article, we discuss the management of motor symptoms during the early phases of Parkinson's disease, excluding that of any other clinical manifestation. We relied primarily upon recently published data and do not describe older publications relating to anticholinergic drugs or amantadine. The initial pharmacological treatment of idiopathic Parkinson's disease (IPD) is symptomatic and remains based upon dopaminergic drugs. However, the development of new drugs has broadened the range of strategic options and improved overall patient management. Announcing the diagnosis is a critical moment, as pointed out by patients' associations. Patients should be advised to maintain personal, professional, social and physical activities as long as possible. The potential benefit of early pharmacological treatment should be explained, focusing on the possible disease-modifying effect of drugs such as rasagiline. According to current guidelines, L-Dopa is preferred in patients above 65years of age, while those below 65 should be treated with dopamine agonists. Like monoamine oxidase inhibitors B (MAOI-B), synthetic dopamine agonists exhibit several advantages: easy-to-use treatment with a once-daily administration, delayed L-Dopa initiation, significant efficacy on motor symptoms (although lower than that of L-Dopa). MOAI can be prescribed in association with L-Dopa or dopamine agonists. Rasagiline also delays L-Dopa initiation, and consequently motor complications. PMID:24673985

  18. Investigation into the dosage form attributes of currently UK licensed cardiovascular and Parkinson's disease drug products.

    PubMed

    Hanning, S M; Muhamed, J; Orlu-Gul, M

    2015-02-01

    Globally, there is a continuous rise in the older population (over 65 years), particularly in developed countries. As many diseases are age-related, older adults represent a highly heterogeneous cohort. This presents a major challenge for both the pharmaceutical industry and healthcare professionals. The purpose of this research was to attract attention towards the appropriateness of geriatric formulations by investigating the dosage form attributes of currently UK licensed cardiovascular and Parkinson's disease drug products. Medication available in the UK for cardiovascular disorders and Parkinson's disease were screened and the available formulations, packaging and patient information leaflets of these medicines were analysed, with the goal of raising awareness of the need to cater for elderly patients with increasing difficulty in managing their medication. It emerged that although cardiovascular disorders and Parkinson's disease are more prevalent in older people, many treatment options have not been optimised for this cohort. In particular, older patient centred dosage forms, specific dosing requirements, excipients, patient-friendly packaging and easy-to-follow patient information were highlighted as areas to be considered in order to optimise health outcomes in the ageing population. PMID:25556052

  19. Levetiracetam attenuates rotenone-induced toxicity: A rat model of Parkinson's disease.

    PubMed

    Erbaş, Oytun; Yılmaz, Mustafa; Taşkıran, Dilek

    2016-03-01

    Levetiracetam (LEV), a second-generation anti-epileptic drug, is used for treatment of both focal and generalized epilepsy. Growing body of evidence suggests that LEV may have neuroprotective effects. The present study was undertaken to investigate the neuroprotective effects of LEV on rotenone-induced Parkinson's disease (PD) in rats. Twenty-four adult Sprague-Dawley rats were infused with rotenone (3 μg/μl in DMSO) or vehicle (1 μl DMSO) into the left substantia nigra pars compacta (SNc) under stereotaxic surgery. PD model was assessed by rotational test ten days after drug infusion. The valid PD rats were randomly distributed into two groups; Group 1 (n=8) and Group 2 (n=8) were administered saline (1 ml/kg/day, i.p.) and LEV (600 mg/kg/day, i.p.) through 21 days, respectively. The effects of LEV treatment were evaluated by behavioral (rotation score), biochemical (brain homovalinic acid level and oxidant/antioxidant status) and immunohistochemical (tyrosine hydroxylase) parameters. Apomorphine-induced rotations in PD rats were significantly suppressed by LEV treatment. While unilateral rotenone lesion induced a dramatic loss of dopaminergic neurons both in the striatum and SNc, LEV treatment significantly attenuated the degenerative changes in dopaminergic neurons. Furthermore, LEV significantly decreased lipid peroxide levels, a marker of lipid peroxidation, and induced glutathione levels, catalase and superoxide dismutase activity in PD rats compared with saline group. We conclude that LEV may have beneficial effects on dopaminergic neurons against rotenone-induced injury. The underlying mechanism may be associated with the attenuation of oxidative stress. PMID:26896611

  20. Dopamine transporter availability in motor subtypes of de novo drug-naïve Parkinson's disease.

    PubMed

    Moccia, Marcello; Pappatà, Sabina; Picillo, Marina; Erro, Roberto; Coda, Anna Rita Daniela; Longo, Katia; Vitale, Carmine; Amboni, Marianna; Brunetti, Arturo; Capo, Giuseppe; Salvatore, Marco; Barone, Paolo; Pellecchia, Maria Teresa

    2014-11-01

    Tremor dominant (TD) and akinetic-rigid type (ART) are two motor subtypes of Parkinson's disease associated with different disease progression and neurochemical/neuropathological features. The role of presynaptic nigrostriatal dopaminergic damage is still controversial, poorly explored, and only assessed in medicated patients. In this study, we investigated with FP-CIT SPECT the striatal dopamine transporter (DAT) availability in drug-naïve PD patients with ART and TD phenotypes. Fifty-one de novo, drug-naïve patients with PD underwent FP-CIT SPECT studies. Patients were evaluated with Unified Parkinson's Disease Rating Scale (UPDRS) part III and Hoehn and Yahr scale (H&Y) and divided into ART (24/51) and TD (27/51) according to UPDRS part III. ART and TD patients were not different with regard to age, gender, and disease duration. However, compared to TD, ART patients presented higher UPDRS part III (p = 0.01) and H&Y (p = 0.02) and lower DAT availability in affected and unaffected putamen (p = 0.008 and p = 0.007, respectively), whereas no differences were found in caudate. Moreover, in the whole group of patients, rigidity and bradykinesia, but not tremor scores of UPDRS part III were significantly related to FP-CIT binding in the putamen. These results suggest that in newly diagnosed drug-naïve PD patients DAT availability might be different between ART and TD in relation to different disease severity. PMID:25119838

  1. The Progress of Induced Pluripotent Stem Cells as Models of Parkinson's Disease

    PubMed Central

    Kang, Ji-feng; Tang, Bei-sha; Guo, Ji-feng

    2016-01-01

    In recent years, induced pluripotent stem cells (iPSCs) were widely used for investigating the mechanisms of Parkinson's disease (PD). Somatic cells from patients with SNCA (α-synuclein), LRRK2 (leucine-rich repeat kinase 2), PINK1 (PTEN induced putative kinase 1), Parkin mutations, and at-risk individuals carrying GBA (β-glucocerebrosidase) mutations have been successfully induced to iPSCs and subsequently differentiated into dopaminergic (DA) neurons. Importantly, some PD-related cell phenotypes, including α-synuclein aggregation, mitophagy, damaged mitochondrial DNA, and mitochondrial dysfunction, have been described in these iPSCs models, which further investigated the pathogenesis of PD. In 2007, Takahashi et al. and Vodyanik et al. generated iPSCs from human somatic cells for the first time. Since then, patients derived iPSCs were applied for disease modeling, drug discovery and screening, autologous cell replacement therapy, and other biological applications. iPSC research has now become a hot topic in a wide range of fields. This review summarizes the recent progress of PD patients derived iPSC models in pathogenic mechanism investigation and potential clinical applications, especially their promising strategy in pharmacological study and DA neurons transplantation therapy. However, the challenges of iPSC transplantation still exist, and it has a long way to go before it can be used in clinical application. PMID:26880962

  2. Duration of drug action of dopamine D2 agonists in mice with 6-hydroxydopamine-induced lesions.

    PubMed

    Tsuchioka, Akihiro; Oana, Fumiki; Suzuki, Takayuki; Yamauchi, Yuji; Ijiro, Tomoyuki; Kaidoh, Kouichi; Hiratochi, Masahiro

    2015-12-16

    Although 6-hydroxydopamine-induced (6-OHDA-induced) rats are a well-known Parkinson's disease model, the effects of dopamine D2 agonists in mice with 6-OHDA-induced lesions are not completely understood. We produced mice with 6-OHDA-induced lesions and measured their total locomotion counts following administration of several dopamine D2 agonists (pramipexole, ropinirole, cabergoline, rotigotine, apomorphine, talipexole, and quinelorane). Cabergoline showed the longest duration of drug action, which was in agreement with its long-lived anti-Parkinson effects in rats and humans. In contrast, pramipexole and ropinirole had notably short durations of drug action. We demonstrated that mice with 6-OHDA-induced lesions accompanied with significant lesions in the striatum may be reasonable models to predict the action duration of anti-Parkinson drug candidates in humans. PMID:26559726

  3. Clinical Features, Pathophysiology, and Treatment of Levodopa-Induced Dyskinesias in Parkinson's Disease

    PubMed Central

    Guridi, J.; González-Redondo, R.; Obeso, J. A.

    2012-01-01

    Dyskinetic disorders are characterized by excess of motor activity that may interfere with normal movement control. In patients with Parkinson's disease, the chronic levodopa treatment induces dyskinetic movements known as levodopa-induced dyskinesias (LID). This paper analyzed the pathophysiology, clinical manifestations, pharmacological treatments, and surgical procedures to treat hyperkinetic disorders. Surgery is currently the only treatment available for Parkinson's disease that may improve both parkinsonian motor syndrome and LID. However, this paper shows the different mechanisms involved are not well understood. PMID:23125942

  4. Drug-induced epistaxis?

    PubMed Central

    Watson, M G; Shenoi, P M

    1990-01-01

    To assess the aetiological contribution made to spontaneous epistaxis in adults over the age of 50 years by various groups of drugs, a controlled study was designed. Fifty-three consecutive epistaxis patients were compared with 50 controls. Significant differences were found between the groups in their consumption of warfarin, dipyridamole and non-steroidal anti-inflammatory drugs. Hypertension was equally common in the two groups, but tended to be less well controlled in the epistaxis patients compared to the controls. It is thought that the link between the use of nonsteroidal anti-inflammatory drugs and the occurrence of epistaxis may be due to alteration of platelet function. PMID:2325058

  5. Drug-induced pulmonary disease

    MedlinePlus

    ... improve. Some drug-induced lung diseases, such as pulmonary fibrosis, may never go away. ... Complications that may develop include: Diffuse interstitial pulmonary fibrosis Hypoxemia (low blood oxygen) Respiratory failure

  6. Drug-induced pancreatitis.

    PubMed

    Nitsche, Claudia; Maertin, Sandrina; Scheiber, Jonas; Ritter, Christoph A; Lerch, Markus M; Mayerle, Julia

    2012-04-01

    Drugs are thought to be a rare cause for acute pancreatitis; however 525 different drugs are listed in the World Health Organization (WHO) database suspected to cause acute pancreatitis as a side effect. Many of them are widely used to treat highly prevalent diseases. The true incidence is not entirely clear since only few systematic population based studies exist. The majority of the available data are derived from case reports or case control studies. Furthermore, the causality for many of these drugs remains elusive and for only 31 of these 525 dugs a definite causality was established. Definite proof for causality is defined by the WHO classification if symptoms reoccur upon rechallenge.In the actual algorithm the diagnosis is confirmed if no other cause of acute pancreatitis can be detected, and the patient is taking one of the suspected drugs. PMID:22314811

  7. Drug-induced diarrhea

    MedlinePlus

    Diarrhea associated with medicines ... Nearly all medicines may cause diarrhea as a side effect. The drugs listed below, however, are more likely to cause diarrhea. Laxatives are meant to cause diarrhea. ...

  8. Drug-induced diarrhea

    MedlinePlus

    Diarrhea associated with medications ... Nearly all medicines may cause diarrhea as a side effect. The drugs listed below, however, are more likely to cause diarrhea. Laxatives are meant to cause diarrhea. ...

  9. Tenofovir induced lichenoid drug eruption

    PubMed Central

    Gupta, Mrinal; Gupta, Heena; Gupta, Anish

    2015-01-01

    Cutaneous adverse reactions are a common complication of anti-retroviral therapy. Tenofovir is a newer anti-retroviral drug belonging to the nucleotide reverse transcriptase inhibitor group. Systemic adverse effects like nausea, vomiting, diarrhea, hepatotoxicity and renal toxicity are common with tenofovir but cutaneous adverse effects are rare. Lichenoid drug eruptions are a common adverse effect seen with a large variety of drugs including antimalarials, antihypertensives, nonsteroidal anti-inflammatory drugs and diuretics. Lichenoid drug eruption is a rare cutaneous adverse effect of tenofovir with only a single case reported till date. Here, we report a case of tenofovir induced lichenoid drug eruption in a 54-year-old human immunodeficiency virus affected male who presented with generalized lichenoid eruption after 6 weeks of initiation of tenofovir and complete clearance on cessation of the drug. PMID:26229762

  10. Inducible nitric oxide synthase gene methylation and parkinsonism in manganese-exposed welders

    PubMed Central

    Nielsen, Susan Searles; Checkoway, Harvey; Criswell, Susan R.; Farin, Federico M.; Stapleton, Patricia L.; Sheppard, Lianne; Racette, Brad A.

    2015-01-01

    Introduction Neurologist-assessed parkinsonism signs are prevalent among workers exposed to manganese (Mn)-containing welding fume. Neuroinflammation may possibly play a role. Inducible nitric oxide synthase, coded by NOS2, is involved in inflammation, and particulate exposure increases the gene’s expression through methylation of CpG sites in the 5′ region. Methods We assessed DNA methylation at three CpG sites in the NOS2 exon 1 from blood from 201 welders. All were non-Hispanic Caucasian men 25–65 years old who were examined by a neurologist specializing in movement disorders. We categorized the workers according to their Unified Parkinson Disease Rating Scale motor subsection 3 (UPDRS3) scores as parkinsonism cases (UPDRS3 ≥ 15; n = 49), controls (UPDRS3 < 6; n = 103), or intermediate (UPDRS3 ≥6 to <15; n = 49). Results While accounting for age, examiner and experimental plate, parkinsonism cases had lower mean NOS2 methylation than controls (p-value for trend = 0.04), specifically at CpG site 8329 located in an exonic splicing enhancer of NOS2 (p-value for trend = 0.07). These associations were not observed for the intermediate UPDRS3 group (both p-value for trend ≥ 0.59). Conclusions Inflammation mediated by inducible nitric oxide synthase may possibly contribute to the association between welding fume and parkinsonism, but requires verification in a longitudinal study. PMID:25634431

  11. Induced pluripotent stem cells in Parkinson's disease: scientific and clinical challenges

    PubMed Central

    Xiao, Bin; Ng, Huck Hui; Takahashi, Ryosuke; Tan, Eng-King

    2016-01-01

    Induced pluripotent stem cells (iPSCs), which greatly circumvent the ethical issue of human embryonic stem cells (ESCs), can be induced to differentiate to dopaminergic (DA) neurons, and hence be used as a human disease model for Parkinson's disease (PD). iPSCs can be also utilised to probe the mechanism, and serve as an ‘in vivo’ platform for drug screening and for cell-replacement therapies. However, any clinical trial approaches should be extensively supported by validated robust biological evidence (based on previous experience with fetal mesencephalic transplantation), in particular, the production and selection of the ‘ideal’ neurons (functional units with no oncological risk), together with the careful screening of appropriate candidates (such as genetic carriers), with inbuilt safeguards (safety studies) in the evaluation and monitoring (functional neuroimaging of both DA and non-DA system) of trial subjects. While iPSCs hold great promise for PD, there are still numerous scientific and clinical challenges that need to be surmounted before any clinical application can be safely introduced. PMID:26833176

  12. Induced pluripotent stem cells in Parkinson's disease: scientific and clinical challenges.

    PubMed

    Xiao, Bin; Ng, Huck Hui; Takahashi, Ryosuke; Tan, Eng-King

    2016-07-01

    Induced pluripotent stem cells (iPSCs), which greatly circumvent the ethical issue of human embryonic stem cells (ESCs), can be induced to differentiate to dopaminergic (DA) neurons, and hence be used as a human disease model for Parkinson's disease (PD). iPSCs can be also utilised to probe the mechanism, and serve as an 'in vivo' platform for drug screening and for cell-replacement therapies. However, any clinical trial approaches should be extensively supported by validated robust biological evidence (based on previous experience with fetal mesencephalic transplantation), in particular, the production and selection of the 'ideal' neurons (functional units with no oncological risk), together with the careful screening of appropriate candidates (such as genetic carriers), with inbuilt safeguards (safety studies) in the evaluation and monitoring (functional neuroimaging of both DA and non-DA system) of trial subjects. While iPSCs hold great promise for PD, there are still numerous scientific and clinical challenges that need to be surmounted before any clinical application can be safely introduced. PMID:26833176

  13. Drug-induced pseudolupus.

    PubMed

    Grob, P J; Müller-Schoop, J W; Häcki, M A; Joller-Jemelka, H I

    1975-07-26

    Of fifteen patients with pseudolupus (a syndrome characterised by recurrent fever, myalgia, arthralgia, pleuritis, pulmonary infiltrates, pericarditis, myocarditis, and by mitochondrial antibodies in the absence of nuclear antibodies), all had been treated with "Venocuran", one of a great number of drugs used for venous diseases. This drug, available in twenty countries under various names, contains phenopyrazone, horse-chestnut extract, and cardiac glycosides extracted from various plants. Further studies revealed that up to 90% of long-term users of venocuran acquired mitochondrial antibodies. This was not true for patients with venous diseases being treated with other drugs. About 30% of long-term users of venocuran might experience prodronal symptoms, such as myalgia and arthralgia, while more than 10% could develop the full disease. PMID:49743

  14. Multi-Drug-Loaded Microcapsules with Controlled Release for Management of Parkinson's Disease.

    PubMed

    Baek, Jong-Suep; Choo, Chee Chong; Qian, Cheng; Tan, Nguan Soon; Shen, Zexiang; Loo, Say Chye Joachim

    2016-07-01

    Parkinson's disease (PD) is a progressive disease of the nervous system, and is currently managed through commercial tablets that do not sufficiently enable controlled, sustained release capabilities. It is hypothesized that a drug delivery system that provides controlled and sustained release of PD drugs would afford better management of PD. Hollow microcapsules composed of poly-l-lactide (PLLA) and poly (caprolactone) (PCL) are prepared through a modified double-emulsion technique. They are loaded with three PD drugs, i.e., levodopa (LD), carbidopa (CD), and entacapone (ENT), at a ratio of 4:1:8, similar to commercial PD tablets. LD and CD are localized in both the hollow cavity and PLLA/PCL shell, while ENT is localized in the PLLA/PCL shell. Release kinetics of hydrophobic ENT is observed to be relatively slow as compared to the other hydrophilic drugs. It is further hypothesized that encapsulating ENT into PCL as a surface coating onto these microcapsules can aid in accelerating its release. Now, these spray-coated hollow microcapsules exhibit similar release kinetics, according to Higuchi's rate, for all three drugs. The results suggest that multiple drug encapsulation of LD, CD, and ENT in gastric floating microcapsules could be further developed for in vivo evaluation for the management of PD. PMID:27253884

  15. Drug-induced nail disorders.

    PubMed

    2014-07-01

    Nail disorders are defined according to their appearance and the part of the nail affected: the nail plate, the tissues that support or hold the nail plate in place, or the lunula. The consequences of most nail disorders are purely cosmetic. Other disorders, such as ingrown nails, inflammation, erythema, abscesses or tumours, cause functional impairment or pain. The appearance of the lesions is rarely indicative of their cause. Possible causes include physiological changes, local disorders or trauma, systemic conditions, toxic substances and drugs. Most drug-induced nail disorders resolve after discontinuation of the drug, although complete resolution sometimes takes several years. Drugs appear to induce nail disorders through a variety of mechanisms. Some drugs affect the nail matrix epithelium, the nail bed or the nail folds. Some alter nail colour. Other drugs induce photosensitivity. Yet others affect the blood supply to the nail unit. Nail abnormalities are common during treatment with certain cytotoxic drugs: taxanes, anthracyclines, fluorouracil, EGFR, tyrosine kinase inhibitors, etc. Some drugs are associated with a risk of serious and painful lesions, such as abscesses. When these disorders affect quality of life, the benefits of withdrawing the drug must be weighed against the severity of the condition being treated and the drug's efficacy, taking into account the harm-benefit balance of other options. Various anti-infective drugs, including tetracyclines, quinolones, clofazimine and zidovudine, cause the nail plate to detach from the nail bed after exposure to light, or cause nail discoloration. Psoralens and retinoids can also have the same effects. PMID:25162091

  16. Drug-Induced Urinary Calculi

    PubMed Central

    Matlaga, Brian R; Shah, Ojas D; Assimos, Dean G

    2003-01-01

    Urinary calculi may be induced by a number of medications used to treat a variety of conditions. These medications may lead to metabolic abnormalities that facilitate the formation of stones. Drugs that induce metabolic calculi include loop diuretics; carbonic anhydrase inhibitors; and laxatives, when abused. Correcting the metabolic abnormality may eliminate or dramatically attenuate stone activity. Urinary calculi can also be induced by medications when the drugs crystallize and become the primary component of the stones. In this case, urinary supersaturation of the agent may promote formation of the calculi. Drugs that induce calculi via this process include magnesium trisilicate; ciprofloxacin; sulfa medications; triamterene; indinavir; and ephedrine, alone or in combination with guaifenesin. When this situation occurs, discontinuation of the medication is usually necessary. PMID:16985842

  17. Potential sex differences in nonmotor symptoms in early drug-naive Parkinson disease

    PubMed Central

    Umbach, David M.; Peddada, Shyamal D.; Xu, Zongli; Tröster, Alexander I.; Huang, Xuemei; Chen, Honglei

    2015-01-01

    Objective: To examine potential sex differences in nonmotor symptoms (NMS) among drug-naive patients with Parkinson disease (PD), and to identify NMS that can best differentiate patients with early PD from controls. Methods: Our cross-sectional analysis included 414 newly diagnosed, untreated patients with PD (269 men and 145 women) and 188 healthy controls (121 men and 67 women) in the Parkinson's Progression Markers Initiative Study. NMS were measured using well-validated instruments covering sleep, olfactory, neurobehavioral, autonomic, and neuropsychological domains. Results: Male and female patients with PD were fairly comparable on motor presentations but differed on several nonmotor features. Male patients with PD had significantly more pronounced deficits in olfaction (p = 0.02) and in certain cognitive measurements (all p < 0.01) than female patients, whereas female cases experienced higher trait anxiety (p = 0.02). Multiple stepwise logistic regression analysis showed that the combination of NMS measures—University of Pennsylvania Smell Identification Test (UPSIT), Montreal Cognitive Assessment (MoCA), Scales for Outcomes in Parkinson's Disease–Autonomic (SCOPA-AUT), and state anxiety from the State-Trait Anxiety Inventory—effectively differentiated patients with PD from controls with an area under the receiver operating characteristic curve (AUC) of 0.913 (95% confidence interval [CI]: 0.89–0.94). UPSIT, MoCA, and SCOPA-AUT were the most predictive NMS measurements in men (AUC = 0.919; 95% CI: 0.89–0.95) as compared to UPSIT, MoCA, and REM Sleep Behavior Disorder Screening Questionnaire in women (AUC = 0.903; 95% CI: 0.86–0.95). Conclusions: Our analysis revealed notable sex differences in several nonmotor features of patients with de novo PD. Furthermore, we found a parsimonious NMS combination that could effectively differentiate de novo cases from healthy controls. PMID:25925983

  18. Drug-induced hepatitis

    MedlinePlus

    ... induced hepatitis. Painkillers and fever reducers that contain acetaminophen are a common cause of liver inflammation. These ... problem. However, if you took high doses of acetaminophen , treatment should be started as soon as possible ...

  19. Pramipexole- and methamphetamine-induced reward-mediated behavior in a rodent model of Parkinson's disease and controls.

    PubMed

    Riddle, J L; Rokosik, S L; Napier, T C

    2012-07-15

    Pramipexole (PPX) is a dopamine agonist that is FDA-approved for treatment of motor dysfunction in Parkinson's disease and restless leg syndrome. In a subpopulation of treated patients, PPX can lead to impulsive-compulsive disorders including behavioral addictions and dopamine dysregulation syndrome, a phenomenon that mirrors drug addiction. Regardless of this clinical picture, the capacity of PPX to regulate reward-mediated behaviors remains unclear and has not been evaluated in an animal model of Parkinson's disease. To fill this gap, we examined the rewarding potential of PPX in parkinsonian-like rats using conditioned place preference (CPP) and also evaluated associated motor behaviors. Methamphetamine (meth) and saline served as positive and negative controls, respectively. To model Parkinson's disease, the neurotoxin 6-OHDA was injected bilaterally into the dorsolateral striatum. The resulting lesions were verified functionally using a forelimb adjusting step and post mortem immunohistochemical staining of striatal tyrosine hydroxylase. Three pairings of meth (1mg/kg, ip), paired with a unique context, induced CPP in both 6-OHDA-treated and sham-operated rats; saline pairings had no effect. Three pairings of (±)PPX at 2mg/kg ip (equal to 1mg/kg of the active racimer) induced CPP in 6-OHDA-treated rats, but a higher dose (4 mg/kg, ip (±)PPX) was needed to induce CPP in sham rats. In all rats, acute administration of 2mg/kg (±)PPX decreased locomotor activity; the behavior was normalized by the third (±)PPX administration. In summary, these findings reveal that (±)PPX has motor and rewarding effects and suggest the parkinsonian brain state may be more sensitive to the rewarding, but not motoric effects. PMID:22727039

  20. Novel neuroprotective mechanisms of pramipexole, an anti-Parkinson drug, against endogenous dopamine-mediated excitotoxicity.

    PubMed

    Izumi, Yasuhiko; Sawada, Hideyuki; Yamamoto, Noriyuki; Kume, Toshiaki; Katsuki, Hiroshi; Shimohama, Shun; Akaike, Akinori

    2007-02-28

    Parkinson disease is characterized by selective degeneration of mesencephalic dopaminergic neurons, and endogenous dopamine may play a pivotal role in the degenerative processes. Using primary cultured mesencephalic neurons, we found that glutamate, an excitotoxin, caused selective dopaminergic neuronal death depending on endogenous dopamine content. Pramipexole, a dopamine D2/D3 receptor agonist used clinically in the treatment of Parkinson disease, did not affect glutamate-induced calcium influx but blocked dopaminergic neuronal death induced by glutamate. Pramipexole reduced dopamine content but did not change the levels of total or phosphorylated tyrosine hydroxylase, a rate-limiting enzyme in dopamine synthesis. The neuroprotective effect of pramipexole was independent of dopamine receptor stimulation because it was not abrogated by domperidone, a dopamine D2-type receptor antagonist. Moreover, both active S(-)- and inactive R(+)-enantiomers of pramipexole as a dopamine D2-like receptor agonist equally suppressed dopaminergic neuronal death. These results suggest that pramipexole protects dopaminergic neurons from glutamate neurotoxicity by the reduction of intracellular dopamine content, independently of dopamine D2-like receptor activation. PMID:17161393

  1. Levodopa-induced plasticity: a double-edged sword in Parkinson's disease?

    PubMed Central

    Calabresi, Paolo; Ghiglieri, Veronica; Mazzocchetti, Petra; Corbelli, Ilenia; Picconi, Barbara

    2015-01-01

    The long-term replacement therapy with the dopamine (DA) precursor 3,4-dihydroxy-l-phenylalanine (L-DOPA) is a milestone in the treatment of Parkinson's disease (PD). Although this drug precursor can be metabolized into the active neurotransmitter DA throughout the brain, its therapeutic benefit is due to restoring extracellular DA levels within the dorsal striatum, which lacks endogenous DA as a consequence of the neurodegenerative process induced by the disease. In the early phases of PD, L-DOPA treatment is able to restore both long-term depression (LTD) and long-term potentiation (LTP), two major forms of corticostriatal synaptic plasticity that are altered by dopaminergic denervation. However, unlike physiological DA transmission, this therapeutic approach in the advanced phase of the disease leads to abnormal peaks of DA, non-synaptically released, which are supposed to trigger behavioural sensitization, namely L-DOPA-induced dyskinesia. This condition is characterized by a loss of synaptic depotentiation, an inability to reverse previously induced LTP. In the advanced stages of PD, L-DOPA can also induce non-motor fluctuations with cognitive dysfunction and neuropsychiatric symptoms such as compulsive behaviours and impulse control disorders. Although the mechanisms underlying the role of L-DOPA in both motor and behavioural symptoms are still incompletely understood, recent data from electrophysiological and imaging studies have increased our understanding of the function of the brain areas involved and of the mechanisms implicated in both therapeutic and adverse actions of L-DOPA in PD patients. PMID:26009763

  2. Psychotropic drug-induced neutropenia.

    PubMed

    Duggal, Harpreet S; Singh, Ira

    2005-08-01

    Psychotropic medications have been known to cause blood dyscrasias, including neutropenia, and since the advent of clozapine, this side effect is now increasingly being recognized. Almost all the major classes of psychotropic medications have been associated with neutropenia. Operational definitions for blood dyscrasias have allowed us to create an epidemiological database on this rare side effect of psychotropic medications. With increased awareness of drug-induced neutropenia among physicians, methods of early detection and treatment of this side effect have also been the focus of recent literature. Another area of active research has been identifying the risk factors and mechanism of drug-induced neutropenia. This article attempts to synthesize our current understanding of psychotropic drug-induced neutropenia and also provide insights into future research in this realm. PMID:16234875

  3. Vanillin Attenuated Behavioural Impairments, Neurochemical Deficts, Oxidative Stress and Apoptosis Against Rotenone Induced Rat Model of Parkinson's Disease.

    PubMed

    Dhanalakshmi, Chinnasamy; Janakiraman, Udaiyappan; Manivasagam, Thamilarasan; Justin Thenmozhi, Arokiasamy; Essa, Musthafa Mohamed; Kalandar, Ameer; Khan, Mohammed Abdul Sattar; Guillemin, Gilles J

    2016-08-01

    Vanillin (4-hydroxy-3-methoxybenzaldehyde), a pleasant smelling organic aromatic compound, is widely used as a flavoring additive in food, beverage, cosmetic and drug industries. It is reported to cross the blood brain barrier and also displayed antioxidant and neuroprotective activities. We previously reported the neuroprotective effect of vanillin against rotenone induced in in vitro model of PD. The present experiment was aimed to analyze the neuroprotective effect of vanillin on the motor and non-motor deficits, neurochemical variables, oxidative, anti-oxidative indices and the expression of apoptotic markers against rotenone induced rat model of Parkinson's disease (PD). Rotenone treatment exhibited motor and non-motor impairments, neurochemical deficits, oxidative stress and apoptosis, whereas oral administration of vanillin attenuated the above-said indices. However further studies are needed to explore the mitochondrial protective and anti-inflammatory properties of vanillin, as these processes play a vital role in the cause and progression of PD. PMID:27038927

  4. Behavioral dysfunction in Parkinson's disease.

    PubMed

    Friedman, J H

    1998-01-01

    Behavioral manifestations of Parkinson's disease (PD) are often more debilitating than the motor manifestations. These occur both as primary manifestations of the disease and as drug-induced complications. While dementia and abulia are common problems that are not currently treatable, depression and psychosis often respond extremely well to medication. Phenomenology, pathology, and general approaches to treatment will be discussed. PMID:10785833

  5. Drugs induced pulmonary arterial hypertension.

    PubMed

    Seferian, Andrei; Chaumais, Marie-Camille; Savale, Laurent; Günther, Sven; Tubert-Bitter, Pascale; Humbert, Marc; Montani, David

    2013-09-01

    Pulmonary arterial hypertension (PAH) is a rare disorder characterized by progressive obliteration of the pulmonary microvasculature, resulting in elevated pulmonary vascular resistance and premature death. According to the current classification, PAH can be associated with exposure to certain drugs or toxins, particularly appetite suppressant drugs, such as aminorex, fenfluramine derivatives and benfluorex. These drugs have been confirmed to be risk factors for PAH and were withdrawn from the market. The supposed mechanism is an increase in serotonin levels, which was demonstrated to act as a growth factor for the pulmonary arterial smooth muscle cells. Amphetamines, phentermine and mazindol were less frequently used but are also considered as possible risk factors for PAH. Dasatinib, a dual Src/Abl kinase inhibitor, used in the treatment of chronic myelogenous leukaemia was associated with cases of severe PAH, in part reversible after its withdrawal. Recently several studies raised the potential endothelial dysfunction that could be induced by interferon, and few cases of PAH have been reported with interferon therapy. Other possible risk factors for PAH include: nasal decongestants, like phenylpropanolamine, dietary supplement - L-Tryptophan, selective serotonin reuptake inhibitors, pergolide and other drugs that could act on 5HT2B receptors. Interestingly, PAH remains a rare complication of these drugs, suggesting possible individual susceptibility and further studies are needed to identify patients at risk of drugs induced PAH. PMID:23972547

  6. Identification of potential drugs for Parkinson's disease based on a sub-pathway method.

    PubMed

    Sun, Ai-Guo; Lin, Ai-Qi; Huang, Shao-Yue; Huo, Di; Cong, Chao-Hua

    2016-01-01

    Parkinson's disease (PD) is the second most prevalent neurodegenerative disease in ageing individuals. Current therapeutic regimen suffers from general side effects and a poor efficiency for PD symptoms. The need for development new therapeutic agents for PD is urgent. Here, we aimed to explore the metabolic mechanism of PD and identified potential novel agents for PD by a sub-pathway-based method. By using the GSE7621 microarray data from the GEO database, we first identified the 1226 differentially expressed genes (DEGs) between PD and normal samples. Then we identified 19 significant enriched metabolic sub-pathways, which may involve in development of PD. Finally, by an integrated analysis of PD-involved sub-pathways and drug-affected sub-pathways, we identified 49 novel small molecular drugs capable to target the PD-involved sub-pathways. Our method could not only identify existing drug (apomorphine) for PD, but also predict potentially novel agents (ketoconazole and astemizole), which might have therapeutic effects via targeting some key enzymes in arachidonic acid metabolism. These candidate agents identified by our approach may provide insights into a novel therapy approach for PD. PMID:25405535

  7. [Drug-induced Cognitive Impairment].

    PubMed

    Shinohara, Moeko; Yamada, Masahito

    2016-04-01

    Elderly people are more likely than young people to develop cognitive impairments associated with medication use. One of the reasons for this is that renal and liver functions are often impaired in elderly people. Dementia and delirium (an acute confused state) are known to be associated with drug toxicity. Anticholinergic medications are common causes of both acute and chronic cognitive impairment. Psychoactive drugs, antidepressants and anticonvulsants can cause dementia and delirium. In addition, non-psychoactive drugs such as histamine H2 receptor antagonists, corticosteroids, NSAIDs (nonsteroidal anti-inflammatory agent), and cardiac medications, may cause acute or chronic cognitive impairment. Early diagnosis and withdrawal of the offending agent are essential for the prevention of drug-induced dementia and delirium. PMID:27056860

  8. Drug-induced visceral angioedema

    PubMed Central

    Thalanayar, Prashanth M.; Ghobrial, Ibrahim; Lubin, Fritz; Karnik, Reena; Bhasin, Robin

    2014-01-01

    Angioedema associated with angiotensin converting enzyme inhibitors (ACEIs) is due to the accumulation of bradykinin and its metabolites. Angiotensin receptor blockers (ARBs) produce anti-hypertensive effects by blocking the angiotensin II AT1 receptor action; hence bradykinin-related side effects are not expected. However, we notice the occurrence of ARB-induced angioedema as not a very rare side effect. Visceral drug-induced angioedema has been reported with ACEIs, not with ARBs. This underlying review will help educate readers on the pathophysiology and recent guidelines pertaining to ACEI- and ARB-induced visceral angioedema. PMID:25317271

  9. Drug-Path: a database for drug-induced pathways

    PubMed Central

    Zeng, Hui; Cui, Qinghua

    2015-01-01

    Some databases for drug-associated pathways have been built and are publicly available. However, the pathways curated in most of these databases are drug-action or drug-metabolism pathways. In recent years, high-throughput technologies such as microarray and RNA-sequencing have produced lots of drug-induced gene expression profiles. Interestingly, drug-induced gene expression profile frequently show distinct patterns, indicating that drugs normally induce the activation or repression of distinct pathways. Therefore, these pathways contribute to study the mechanisms of drugs and drug-repurposing. Here, we present Drug-Path, a database of drug-induced pathways, which was generated by KEGG pathway enrichment analysis for drug-induced upregulated genes and downregulated genes based on drug-induced gene expression datasets in Connectivity Map. Drug-Path provides user-friendly interfaces to retrieve, visualize and download the drug-induced pathway data in the database. In addition, the genes deregulated by a given drug are highlighted in the pathways. All data were organized using SQLite. The web site was implemented using Django, a Python web framework. Finally, we believe that this database will be useful for related researches. Database URL: http://www.cuilab.cn/drugpath PMID:26130661

  10. Drug-Path: a database for drug-induced pathways.

    PubMed

    Zeng, Hui; Qiu, Chengxiang; Cui, Qinghua

    2015-01-01

    Some databases for drug-associated pathways have been built and are publicly available. However, the pathways curated in most of these databases are drug-action or drug-metabolism pathways. In recent years, high-throughput technologies such as microarray and RNA-sequencing have produced lots of drug-induced gene expression profiles. Interestingly, drug-induced gene expression profile frequently show distinct patterns, indicating that drugs normally induce the activation or repression of distinct pathways. Therefore, these pathways contribute to study the mechanisms of drugs and drug-repurposing. Here, we present Drug-Path, a database of drug-induced pathways, which was generated by KEGG pathway enrichment analysis for drug-induced upregulated genes and downregulated genes based on drug-induced gene expression datasets in Connectivity Map. Drug-Path provides user-friendly interfaces to retrieve, visualize and download the drug-induced pathway data in the database. In addition, the genes deregulated by a given drug are highlighted in the pathways. All data were organized using SQLite. The web site was implemented using Django, a Python web framework. Finally, we believe that this database will be useful for related researches. PMID:26130661

  11. Drug-induced lupus erythematosus.

    PubMed

    Vedove, Camilla Dalle; Del Giglio, Micol; Schena, Donatella; Girolomoni, Giampiero

    2009-01-01

    Drug-induced lupus erythematosus (DILE) is defined as a lupus-like syndrome temporally related to continuous drug exposure which resolves after discontinuation of the offending drug. There are currently no standard diagnostic criteria for DILE and the pathomechanisms are still unclear. Similarly to idiopathic lupus, DILE can be diveded into systemic (SLE), subacute cutaneous (SCLE) and chronic cutaneous lupus (CCLE). Systemic DILE is characterized by typical lupus-like symptoms including skin signs, usually mild systemic involvement and a typical laboratory profile with positive antinuclear and anti-histone antibodies, while anti-double strand (ds) DNA and anti-extractable nuclear antigens antibodies are rare. High risk drugs include hydralazine, procainamide and isoniazid. Drug-induced SCLE is very similar to idiopathic SCLE in terms of clinical and serologic characteristic, and it is more common than the systemic form of DILE. Drugs associated with SCLE include calcium channel blockers, angiotensin-converting enzyme inhibitors, interferons, thiazide diuretics and terbinafine. Drug-induced CCLE is very rarely reported in the literature and usually refers to fluorouracile agents or non steroidal anti-inflammatory drugs. Recently, cases of DILE have been reported with anti-TNFalpha agents. These cases present with disparate clinical features including arthritis/arthralgia, skin rash, serositis, cytopenia and variable laboratory abnormalities. DILE to anti-TNFalpha agents differs in several ways to classic DILE. The incidence of rashes is higher compared to classical systemic DILE. In most cases of classic DILE visceral involvement is rare, whereas several cases of anti-TNFalpha DILE with evidence of renal disease have been reported. Low serum complement levels as well as anti-extractable nuclear antigen antibodies and anti-dsDNA antibodies are rarely present in classic DILE, whereas they are reported in half the cases of anti-TNFalpha DILE; in contrast, anti

  12. Manganese-Induced Parkinsonism and Parkinson’s Disease: Shared and Distinguishable Features

    PubMed Central

    Kwakye, Gunnar F.; Paoliello, Monica M.B.; Mukhopadhyay, Somshuvra; Bowman, Aaron B.; Aschner, Michael

    2015-01-01

    Manganese (Mn) is an essential trace element necessary for physiological processes that support development, growth and neuronal function. Secondary to elevated exposure or decreased excretion, Mn accumulates in the basal ganglia region of the brain and may cause a parkinsonian-like syndrome, referred to as manganism. The present review discusses the advances made in understanding the essentiality and neurotoxicity of Mn. We review occupational Mn-induced parkinsonism and the dynamic modes of Mn transport in biological systems, as well as the detection and pharmacokinetic modeling of Mn trafficking. In addition, we review some of the shared similarities, pathologic and clinical distinctions between Mn-induced parkinsonism and Parkinson’s disease. Where possible, we review the influence of Mn toxicity on dopamine, gamma aminobutyric acid (GABA), and glutamate neurotransmitter levels and function. We conclude with a survey of the preventive and treatment strategies for manganism and idiopathic Parkinson’s disease (PD). PMID:26154659

  13. Optimization of Parkinson Disease treatment combining anti-Parkinson drugs and deep brain stimulation using patient diaries.

    PubMed

    Schneider, Jakub; Novak, Daniel; Jech, Robert

    2015-01-01

    The number of patients suffering from Parkinson's disease is increasing rapidly due to population aging. While traditional medications-based palliative therapy is successful in early stages, deep brain stimulation (DBS) may be used as an alternative treatment in later stages. After DBS implantation, the therapy typically consists of electrical stimulation and reduced medication. In order to provide good clinical outcome, a balance has to be found between medication and stimulation parameters, this is usually done as follows: First, Unified Parkinson's Disease Rating Scale (UPDRS) scoring is performed, second patients are supposed to fill subjective diaries during a specific period. This study shows that these diaries are useful as therapy progression indicator. Feel scores based on diaries and sleep time were examined with respect to DBS stimulation and medication. The results confirmed the positive effect of both therapy components--stimulation as well as medication--on patient feel scores. Furthermore, a positive correlation was observed between stimulation energy and sleep duration. PMID:26737033

  14. Increased reflection impulsivity in patients with ephedrone induced Parkinsonism

    PubMed Central

    Djamshidian, Atbin; Sanotsky, Yanosh; Matviyenko, Yuriy; O’Sullivan, Sean S.; Sharman, Stephen; Selikhova, Marianna; Fedoryshyn, Ludmyla; Filts, Yuriy; Bearn, Jenny; Lees, Andrew J.; Averbeck, Bruno B.

    2012-01-01

    Aims To examine a syndrome of chronic manganism that occurs in drug addicts in Eastern Europe who use intravenous methcathinone (ephedrone) contaminated with potassium permanganate. The basal ganglia, especially the globus pallidus and the putamen, are damaged irreversibly in many cases. Routine neuropsychological assessment has revealed no cognitive deficits despite widespread abnormalities on brain imaging studies and severe extrapyramidal motor handicap on clinical examination. Design Case control study. Setting Ephedrone patients and patients with opioid dependence were recruited from Lviv, Ukraine. Participants We tested 15 patients with ephedrone induced toxicity, 13 opiate dependent patients, who were receiving opioid replacement therapy and 18 matched healthy volunteers. Measurements The ‘beads task’, an information gathering task to assess reflection impulsivity was used and feedback learning, working memory and risk taking were also assessed. Findings Opiate dependent patients differed from controls on three out of four tasks, whereas ephedrone patients differed from controls on only one task. More specifically both patient groups were more impulsive and made more irrational choices on the beads task than controls (p<0.001). However, ephedrone patients had no deficits in working memory (p>0.1) or risk taking (p>0.1) compared with controls. Opioid dependent patients had significantly worse working memory (p<0.001) and were significantly more risk prone than controls (p=0.002). Conclusions Ephedrone patients may have similar deficits in information gathering and decision making to opiate dependent patients, with preservation of working memory and risk taking. This may reflect specific damage to anterior cingulate- basal ganglia loops. PMID:23228208

  15. Differential Dopamine Receptor Occupancy Underlies L-DOPA-Induced Dyskinesia in a Rat Model of Parkinson's Disease

    PubMed Central

    Sahin, Gurdal; Thompson, Lachlan H.; Lavisse, Sonia; Ozgur, Merve; Rbah-Vidal, Latifa; Dollé, Frédéric

    2014-01-01

    Dyskinesia is a major side effect of an otherwise effective L-DOPA treatment in Parkinson's patients. The prevailing view for the underlying presynaptic mechanism of L-DOPA-induced dyskinesia (LID) suggests that surges in dopamine (DA) via uncontrolled release from serotonergic terminals results in abnormally high level of extracellular striatal dopamine. Here we used high-sensitivity online microdialysis and PET imaging techniques to directly investigate DA release properties from serotonergic terminals both in the parkinsonian striatum and after neuronal transplantation in 6-OHDA lesioned rats. Although L-DOPA administration resulted in a drift in extracellular DA levels, we found no evidence for abnormally high striatal DA release from serotonin neurons. The extracellular concentration of DA remained at or below levels detected in the intact striatum. Instead, our results showed that an inefficient release pool of DA associated with low D2 receptor binding remained unchanged. Taken together, these findings suggest that differential DA receptor activation rather than excessive release could be the underlying mechanism explaining LID seen in this model. Our data have important implications for development of drugs targeting the serotonergic system to reduce DA release to manage dyskinesia in patients with Parkinson's disease. PMID:24614598

  16. Gender differences in non-motor symptoms in early, drug naïve Parkinson's disease.

    PubMed

    Picillo, Marina; Amboni, Marianna; Erro, Roberto; Longo, Katia; Vitale, Carmine; Moccia, Marcello; Pierro, Angela; Santangelo, Gabriella; De Rosa, Anna; De Michele, Giuseppe; Santoro, Lucio; Orefice, Giuseppe; Barone, Paolo; Pellecchia, Maria Teresa

    2013-11-01

    Gender differences in brain structure and function may lead to differences in the clinical expression of neurological diseases, including Parkinson's disease (PD). Few studies reported gender-related differences in the burden of non-motor symptoms (NMS) in treated PD patients, but this matter has not been previously explored in drug-naïve PD patients. This study is to assess gender differences in the prevalence of NMS in a large sample of early, drug-naïve PD patients compared with age and sex-matched healthy controls. Two hundred early, drug-naïve PD patients and ninety-three age and sex-matched healthy controls were included in the study. Frequency of NMS was evaluated by means of the Non-Motor Symptoms Questionnaire. The difference in gender distribution of NMS was evaluated with the χ (2) exact test; multiple comparisons were corrected with the Benjamini-Hochberg method. Male PD patients complained of problems having sex and taste/smelling difficulties significantly more frequently than female PD patients. Furthermore, men with PD complained more frequently of dribbling, sadness/blues, loss of interest, anxiety, acting during dreams, and taste/smelling difficulties as compared to healthy control men, while female PD patients reported more frequently loss of interest and anxiety as compared with healthy control women. This study shows specific sex-related patterns of NMS in drug-naïve PD. In contrast with previous data, female PD patients did not present higher prevalence of mood symptoms as compared to male PD patients. Comparison with healthy controls showed that some NMS classically present in premotor and early stage of disease (i.e., acting out during dreams, taste/smelling difficulties) are more frequent in male than in female patients. PMID:23989344

  17. Drug-induced weight gain.

    PubMed

    Ness-Abramof, Rosane; Apovian, Caroline M

    2005-01-01

    Drug-induced weight gain is a serious side effect of many commonly used drugs leading to noncompliance with therapy and to exacerbation of comorbid conditions related to obesity. Improved glycemic control achieved by insulin, insulin secretagogues or thiazolidinedione therapy is generally accompanied by weight gain. It is a problematic side effect of therapy due to the known deleterious effect of weight gain on glucose control, increased blood pressure and worsening lipid profile. Weight gain may be lessened or prevented by adherence to diet and exercise or combination therapy with metformin. Weight gain is also common in psychotropic therapy. The atypical antipsychotic drugs (clozapine, olanzepine, risperidone and quetiapine) are known to cause marked weight gain. Antidepressants such as amitriptyline, mirtazapine and some serotonin reuptake inhibitors (SSRIs) also may promote appreciable weight gain that cannot be explained solely by improvement in depressive symptoms. The same phenomenon is observed with mood stabilizers such as lithium, valproic acid and carbamazepine. Antiepileptic drugs (AEDs) that promote weight gain include valproate, carbamazepine and gabapentin. Lamotrigine is an AED that is weight-neutral, while topiramate and zonisamide may induce weight loss. PMID:16341287

  18. Drug-induced weight gain.

    PubMed

    Ness-Abramof, Rosane; Apovian, Caroline M

    2005-08-01

    Drug-induced weight gain is a serious side effect of many commonly used drugs leading to noncompliance with therapy and to exacerbation of comorbid conditions related to obesity. Improved glycemic control achieved by insulin, insulin secretagogues or thiazolidinedione therapy is generally accompanied by weight gain. It is a problematic side effect of therapy due to the known deleterious effect of weight gain on glucose control, increased blood pressure and worsening lipid profile. Weight gain may be lessened or prevented by adherence to diet and exercise or combination therapy with metformin. Weight gain is also common in psychotropic therapy. The atypical antipsychotic drugs (clozapine, olanzepine, risperidone and quetiapine) are known to cause marked weight gain. Antidepressants such as amitriptyline, mirtazapine and some serotonin reuptake inhibitors (SSRIs) also may promote appreciable weight gain that cannot be explained solely by improvement in depressive symptoms. The same phenomenon is observed with mood stabilizers such as lithium, valproic acid and carbamazepine. Antiepileptic drugs (AEDs) that promote weight gain include valproate, carbamazepine and gabapentin. Lamotrigine is an AED that is weight-neutral, while topiramate and zonisamide may induce weight loss. PMID:16234878

  19. Relationship between the auditory P300 and the procedural memory function in drug-naive patients with Parkinson's disease.

    PubMed

    Kim, G W; Sohn, Y H; Huh, K; Kim, J S

    1995-09-01

    We evaluated and compared procedural memory and auditory P300 event-related potential in age-matched normal controls (n = 15) and drug-naive patients with Parkinson's disease (n = 16). We used Gollin's incomplete picture test for visual procedural memory function and Tower of Hanoi puzzle for visuomotor procedural memory function. The mean latency of P300 was significantly prolonged in the Parkinsonian group than in the controls. In the neuropsychology test, the patients group revealed selective impairment of visuomotor procedural memory against preserved visual procedural memory. In the patients group, the latency of P300 was inversely correlated with performance of visuomotor procedural memory. These results suggest that prolonged auditory P300 event-related potential show the dysfunction of visuomotor procedural memory in the basal ganglia, which appears to be more selectively impaired than visual procedural memory in drug-naive patients with Parkinson's disease. PMID:7483680

  20. Dopamine-induced nonmotor symptoms of Parkinson's disease.

    PubMed

    Park, Ariane; Stacy, Mark

    2011-01-01

    Nonmotor symptoms of Parkinson's disease (PD) may emerge secondary to the underlying pathogenesis of the disease, while others are recognized side effects of treatment. Inevitably, there is an overlap as the disease advances and patients require higher dosages and more complex medical regimens. The non-motor symptoms that emerge secondary to dopaminergic therapy encompass several domains, including neuropsychiatric, autonomic, and sleep. These are detailed in the paper. Neuropsychiatric complications include hallucinations and psychosis. In addition, compulsive behaviors, such as pathological gambling, hypersexuality, shopping, binge eating, and punding, have been shown to have a clear association with dopaminergic medications. Dopamine dysregulation syndrome (DDS) is a compulsive behavior that is typically viewed through the lens of addiction, with patients needing escalating dosages of dopamine replacement therapy. Treatment side effects on the autonomic system include nausea, orthostatic hypotension, and constipation. Sleep disturbances include fragmented sleep, nighttime sleep problems, daytime sleepiness, and sleep attacks. Recognizing the non-motor symptoms that can arise specifically from dopamine therapy is useful to help optimize treatment regimens for this complex disease. PMID:21603184

  1. Dopamine-Induced Nonmotor Symptoms of Parkinson's Disease

    PubMed Central

    Park, Ariane; Stacy, Mark

    2011-01-01

    Nonmotor symptoms of Parkinson's disease (PD) may emerge secondary to the underlying pathogenesis of the disease, while others are recognized side effects of treatment. Inevitably, there is an overlap as the disease advances and patients require higher dosages and more complex medical regimens. The non-motor symptoms that emerge secondary to dopaminergic therapy encompass several domains, including neuropsychiatric, autonomic, and sleep. These are detailed in the paper. Neuropsychiatric complications include hallucinations and psychosis. In addition, compulsive behaviors, such as pathological gambling, hypersexuality, shopping, binge eating, and punding, have been shown to have a clear association with dopaminergic medications. Dopamine dysregulation syndrome (DDS) is a compulsive behavior that is typically viewed through the lens of addiction, with patients needing escalating dosages of dopamine replacement therapy. Treatment side effects on the autonomic system include nausea, orthostatic hypotension, and constipation. Sleep disturbances include fragmented sleep, nighttime sleep problems, daytime sleepiness, and sleep attacks. Recognizing the non-motor symptoms that can arise specifically from dopamine therapy is useful to help optimize treatment regimens for this complex disease. PMID:21603184

  2. Pathogenesis of Mortalin in Manganese-induced Parkinsonism

    NASA Astrophysics Data System (ADS)

    Cook, Travis J.

    Manganese (Mn) is an essential dietary micronutrient for which excessive exposure has long been known to be neurotoxic. Historically, short-term, high-intensity exposure in occupational settings was recognized to cause acute-onset parkinsonism (PS) termed manganism. Although modern day exposures are typically several orders of magnitude lower than those necessary to cause manganism, chronic, low-level exposures are not uncommon among a number of occupations and communities. Recent epidemiologic studies have demonstrated an association between Mn exposure and risk of PS, and in this regard Mn remains a public health concern. The work described here was designed to provide insight toward questions which remain with respect to Mn exposure and its toxic effect on the brain, and includes studies utilizing Mn exposed human populations and in vitro model systems to address these objectives. Blood plasma samples obtained from a cohort of welders, whose work is recognized as generating appreciable amounts of airborne Mn, and post-mortem brain tissue of Mn mine workers were both found to have discernable alterations related to the mitochondrial chaperone protein mortalin. Furthermore, in vitro studies demonstrated that reduced astroglial expression of mortalin confers neuronal susceptibility to toxicity elicited by low levels of Mn, possibly via mechanisms of endoplasmic reticulum and oxidative stress mediated by alpha-synuclein. Taken together, the results of these studies indicate that Mn exposures experienced by modern day populations are sufficient to cause biological alterations in humans that are potentially neurotoxic.

  3. [Drug-induced ventricular tachycardia].

    PubMed

    Fauchier, J P; Fauchier, L; Babuty, D; Breuillac, J C; Cosnay, P; Rouesnel, P

    1993-05-01

    Certain drugs can induce ventricular tachycardia (VT) by creating reentry, ventricular after potentials or exaggerating the slope of phase 4. These may or may not be symptomatic, sustained or non-sustained and have variable ECG appearances: monomorphic or polymorphic, bidirectional, torsades de pointes. They risk degenerating into ventricular flutter of fibrillation and have been held responsible for the increased mortality observed unexpectedly in some long-term treatments. The drugs responsible are mainly those used in cardiology, probably due to predisposing circumstances (cardiomegaly, cardiac failure, previous severe ventricular arrhythmias, therapeutic associations, metabolic abnormalities). These include primarily the antiarrhythmic drugs (IA, IC, sotalol and bepridil), digitalis, sympathomimetics and phosphodiesterase inhibitors. These complications may be toxic or idiosyncratic, in patients with or without cardiac disease, and may also occur with other drugs: vasodilators and anti-anginal drugs (lidoflazine, vincamine, fenoxedil), psychotropic agents (phenothiazine and imipramine), antimitotics, antimalarials (chloroquine) or antibiotics (erythromycin, pentamidine). The prognosis is severe and the treatment is often difficult which makes prevention, helped by repeated surface ECG (or Holter monitoring), very important with careful assessment of patients at risk. PMID:8267504

  4. Secondary parkinsonism

    MedlinePlus

    Parkinsonism - secondary; Atypical Parkinson disease ... to be less responsive to medical therapy than Parkinson disease. ... Unlike Parkinson disease, some types of secondary parkinsonism may stabilize or even improve if the underlying cause is treated. Brain ...

  5. Secondary parkinsonism

    MedlinePlus

    Parkinsonism - secondary; Atypical Parkinson disease ... to be less responsive to medical therapy than Parkinson disease. ... Unlike Parkinson disease, some types of secondary parkinsonism may stabilize or even improve if the underlying cause is treated. ...

  6. Chemoreflex and baroreflex alterations in Parkinsonism induced by 6-OHDA in unanesthetized rats.

    PubMed

    Ariza, Deborah; Lopes, Fernanda Novi Cortegoso; Crestani, Carlos Cesar; Martins-Pinge, Marli Cardoso

    2015-10-21

    Parkinson's disease (PD) is mainly characterized by motor signals. However, non-motor signals also affect and decrease the quality of life of PD patients. Among these non-motor signs are cardiovascular disorders as orthostatic hypotension, postprandial hypotension and cardiac arrhythmias, which may be due to the involvement of both central nervous system and peripheral autonomic nervous system. In the present study we investigated the cardiovascular function, evaluating cardiovascular reflexes (chemoreflex and baroreflex), in an animal model of Parkinsonism induced by bilateral infusion of the toxin 6-hydroxydopamine (6-OHDA), in the substantia nigra pars compacta (SNpc). The results showed that the animals induced to Parkinsonism had lower arterial pressure (AP) and heart rate HR) compared to control animals. We showed that after activation of the baroreceptors by phenylephrine (Phe) and sodium nitroprusside (SNP), the baroreflex sensitivity index was not changed between the groups. However, there was a greater increase in the AP when stimulated with Phe and greater tachycardia when stimulated with SNP in 6-OHDA animals. After activation of the peripheral chemoreceptors through KCN injection (cytotoxic hypoxia), there was a higher increase in pressor and bradycardic response in injured animals with bilateral 6-OHDA. These changes in the cardiovascular reflexes may be important adjustments mechanisms to maintain the cerebral blood flow in those animals, and may be a result of denervation supersensitivity to catecholamines in autonomic targets. PMID:26409036

  7. New drug treatments show neuroprotective effects in Alzheimer's and Parkinson's diseases

    PubMed Central

    Hölscher, Christian

    2014-01-01

    Type 2 diabetes is a risk factor for Alzheimer's disease and Parkinson's disease. Insulin signaling in the brains of people with Alzheimer's disease or Parkinson's disease is impaired. Preclinical studies of growth factors showed impressive neuroprotective effects. In animal models of Alzheimer's disease and Parkinson's disease, insulin, glia-derived neurotrophic factor, or analogues of the incretin glucagon-like peptide-1 prevented neurodegenerative processes and improved neuronal and synaptic functionality in Alzheimer's disease and Parkinson's disease. On the basis of these promising findings, several clinical trials are ongoing with the first encouraging clinical results published. This gives hope for developing effective treatments for Alzheimer's disease and Parkinson's disease that are currently unavailable. PMID:25558231

  8. A drug delivery hydrogel system based on activin B for Parkinson's disease.

    PubMed

    Li, Juan; Darabi, Mohammadali; Gu, Jingjing; Shi, Junbin; Xue, Jinhua; Huang, Lu; Liu, Yutong; Zhang, Lei; Liu, N; Zhong, Wen; Zhang, Lin; Xing, Malcolm; Zhang, Lu

    2016-09-01

    Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Activins are members of the superfamily of transforming growth factors and have many potential neuroprotective effects. Herein, at the first place, we verified activin B's neuroprotective role in a PD model, and revealed that activin B's fast release has limited function in the PD therapy. To this end, we developed a multi-functional crosslinker based thermosensitive injectable hydrogels to deliver activin B, and stereotactically injected the activin B-loaded hydrogel into the striatum of a mouse model of PD. The histological evaluation showed that activin B can be detected even 5 weeks post-surgery in PD mice implanted with activin B-loaded hydrogels, and activin B-loaded hydrogels can significantly increase the density of tyrosine hydroxylase positive (TH(+)) nerve fibers and reduce inflammatory responses. The behavioral evaluation demonstrated that activin B-loaded hydrogels significantly improved the performance of the mice in the PD model. Meanwhile, we found that hydrogels can slightly induce the activation of microglia cells and astrocytes, while cannot induce apoptosis in the striatum. Overall, our data demonstrated that the developed activin B-loaded hydrogels provide sustained release of activin B for over 5 weeks and contribute to substantial cellular protection and behavioral improvement, suggesting their potential as a therapeutic strategy for PD. PMID:27322960

  9. Atropinic (Anticholinergic) Burden in Parkinson's Disease.

    PubMed

    De Germay, Sibylle; Montastruc, Jean-Louis; Rousseau, Vanessa; Chebane, Leila; Bondon-Guitton, Emmanuelle; Moulis, Florence; Durrieu, Genevieve; Bagheri, Haleh; Rascol, Olivier; Pariente, Antoine; Bégaud, Bernard; Montastruc, François

    2016-05-01

    Use of atropinic drugs remains controversial in Parkinson's disease (PD) because there is insufficient evidence about their efficacy and they can induce serious adverse drug reactions. Atropinic risk scales were developed to help to identify atropinic drugs in prescription forms and to evaluate their burden in clinical practice. In the present review, we discuss the few studies investigating atropinic burden in PD and present the results of our study indicating that atropinic drugs are still widely prescribed in PD (almost 3 of 5 prescriptions) with a clinically significant atropinic burden in around 1 of 6 PD patients. Drugs mainly responsible for high values of atropinic burden were those used for nonmotor symptoms. Clinically significant atropinic burdens were mainly induced by associations of several "low-risk" drugs. Physicians must be aware that in addition to classical atropinic antiparkinsonian drugs, many others (psychotropics) can contribute to increased atropinic burden in PD patients. © 2016 International Parkinson and Movement Disorder Society. PMID:27028036

  10. Pathophysiology of Motor Dysfunction in Parkinson's Disease as the Rationale for Drug Treatment and Rehabilitation

    PubMed Central

    Tocco, Pierluigi; Federico, Angela; Zanette, Giampietro

    2016-01-01

    Cardinal motor features of Parkinson's disease (PD) include bradykinesia, rest tremor, and rigidity, which appear in the early stages of the disease and largely depend on dopaminergic nigrostriatal denervation. Intermediate and advanced PD stages are characterized by motor fluctuations and dyskinesia, which depend on complex mechanisms secondary to severe nigrostriatal loss and to the problems related to oral levodopa absorption, and motor and nonmotor symptoms and signs that are secondary to marked dopaminergic loss and multisystem neurodegeneration with damage to nondopaminergic pathways. Nondopaminergic dysfunction results in motor problems, including posture, balance and gait disturbances, and fatigue, and nonmotor problems, encompassing depression, apathy, cognitive impairment, sleep disturbances, pain, and autonomic dysfunction. There are a number of symptomatic drugs for PD motor signs, but the pharmacological resources for nonmotor signs and symptoms are limited, and rehabilitation may contribute to their treatment. The present review will focus on classical notions and recent insights into the neuropathology, neuropharmacology, and neurophysiology of motor dysfunction of PD. These pieces of information represent the basis for the pharmacological, neurosurgical, and rehabilitative approaches to PD. PMID:27366343

  11. Pathophysiology of Motor Dysfunction in Parkinson's Disease as the Rationale for Drug Treatment and Rehabilitation.

    PubMed

    Magrinelli, Francesca; Picelli, Alessandro; Tocco, Pierluigi; Federico, Angela; Roncari, Laura; Smania, Nicola; Zanette, Giampietro; Tamburin, Stefano

    2016-01-01

    Cardinal motor features of Parkinson's disease (PD) include bradykinesia, rest tremor, and rigidity, which appear in the early stages of the disease and largely depend on dopaminergic nigrostriatal denervation. Intermediate and advanced PD stages are characterized by motor fluctuations and dyskinesia, which depend on complex mechanisms secondary to severe nigrostriatal loss and to the problems related to oral levodopa absorption, and motor and nonmotor symptoms and signs that are secondary to marked dopaminergic loss and multisystem neurodegeneration with damage to nondopaminergic pathways. Nondopaminergic dysfunction results in motor problems, including posture, balance and gait disturbances, and fatigue, and nonmotor problems, encompassing depression, apathy, cognitive impairment, sleep disturbances, pain, and autonomic dysfunction. There are a number of symptomatic drugs for PD motor signs, but the pharmacological resources for nonmotor signs and symptoms are limited, and rehabilitation may contribute to their treatment. The present review will focus on classical notions and recent insights into the neuropathology, neuropharmacology, and neurophysiology of motor dysfunction of PD. These pieces of information represent the basis for the pharmacological, neurosurgical, and rehabilitative approaches to PD. PMID:27366343

  12. Drug-Induced Mitochondrial Toxicity.

    PubMed

    Hargreaves, Iain P; Al Shahrani, Mesfer; Wainwright, Luke; Heales, Simon J R

    2016-07-01

    The mitochondrial respiratory chain (MRC) and ATP synthase (complex V) play an essential role in cellular energy production by the process of oxidative phosphorylation. In addition to inborn errors of metabolism, as well as secondary causes from disease pathophysiology, an impairment of oxidative phosphorylation can result from drug toxicity. These 'off-target' pharmacological effects can occur from a direct inhibition of MRC enzyme activity, an induction of mitochondrial oxidative stress, an uncoupling of oxidative phosphorylation, an impairment of mitochondrial membrane structure or a disruption in the replication of mitochondrial DNA. The purpose of this review is to focus on the off-target mitochondrial toxicity associated with both commonly used pharmacotherapies and a topical 'weight loss' agent. The mechanisms of drug-induced mitochondrial impairment will be discussed together with putative therapeutic strategies to counteract the adverse effects of the pharmacotherapy. PMID:26992920

  13. Parkinsonism, tardive dyskinesia, akathisia, and depression induced by flunarizine.

    PubMed

    Chouza, C; Scaramelli, A; Caamaño, J L; De Medina, O; Aljanati, R; Romero, S

    1986-06-01

    12 subjects, 8 women and 4 men, presented with extrapyramidal motor signs and psychic depression after treatment with flunarizine for between 3 weeks and 15 months. One woman presented with severe symptoms and 20 months after stopping flunarizine she still had dyskinesia and akathisia. The other patients showed partial or complete improvement after withdrawal of the drug. PMID:2872433

  14. Potential application of induced pluripotent stem cells in cell replacement therapy for Parkinson's disease.

    PubMed

    Chen, L W; Kuang, F; Wei, L C; Ding, Y X; Yung, K K L; Chan, Y S

    2011-06-01

    Parkinson's disease (PD), a common degenerative disease in humans, is known to result from loss of dopamine neurons in the substantia nigra and is characterized by severe motor symptoms of tremor, rigidity, bradykinsia and postural instability. Although levodopa administration, surgical neural lesion, and deep brain stimulation have been shown to be effective in improving parkinsonian symptoms, cell replacement therapy such as transplantation of dopamine neurons or neural stem cells has shed new light on an alternative treatment strategy for PD. While the difficulty in securing donor dopamine neurons and the immuno-rejection of neural transplants largely hinder application of neural transplants in clinical treatment, induced pluripotent stem cells (iPS cells) derived from somatic cells may represent a powerful tool for studying the pathogenesis of PD and provide a source for replacement therapies in this neurodegenerative disease. Yamanaka et al. [2006, 2007] first succeeded in generating iPS cells by reprogramming fibroblasts with four transcription factors, Oct4, Sox2, Klf4, and c-Myc in both mouse and human. Animal studies have further shown that iPS cells from fibroblasts could be induced into dopamine neurons and transplantation of these cells within the central nervous system improved motor symptoms in the 6-OHDA model of PD. More interestingly, neural stem cells or fibroblasts from patients can be efficiently reprogrammed and subsequently differentiated into dopamine neurons. Derivation of patient-specific iPS cells and subsequent differentiation into dopamine neurons would provide a disease-specific in vitro model for disease pathology, drug screening and personalized stem cell therapy for PD. This review summarizes current methods and modifications in producing iPS cells from somatic cells as well as safety concerns of reprogramming procedures. Novel reprogramming strategies that deter abnormal permanent genetic and epigenetic alterations are essential for

  15. Eltoprazine counteracts l-DOPA-induced dyskinesias in Parkinson's disease: a dose-finding study.

    PubMed

    Svenningsson, Per; Rosenblad, Carl; Af Edholm Arvidsson, Karolina; Wictorin, Klas; Keywood, Charlotte; Shankar, Bavani; Lowe, David A; Björklund, Anders; Widner, Håkan

    2015-04-01

    In advanced stages of Parkinson's disease, serotonergic terminals take up L-DOPA and convert it to dopamine. Abnormally released dopamine may participate in the development of L-DOPA-induced dyskinesias. Simultaneous activation of 5-HT1A and 5-HT1B receptors effectively blocks L-DOPA-induced dyskinesias in animal models of dopamine depletion, justifying a clinical study with eltoprazine, a 5-HT1A/B receptor agonist, against L-DOPA-induced dyskinesias in patients with Parkinson's disease. A double-blind, randomized, placebo-controlled and dose-finding phase I/IIa study was conducted. Single oral treatment with placebo or eltoprazine, at 2.5, 5 and 7.5 mg, was tested in combination with a suprathreshold dose of L-DOPA (Sinemet®) in 22 patients with Parkinson's disease (16 male/six female; 66.6 ± 8.8 years old) with L-DOPA-induced dyskinesias. A Wilcoxon Signed Ranked Test was used to compare each eltoprazine dose level to paired randomized placebo on the prespecified primary efficacy variables; area under the curve scores on Clinical Dyskinesia Rating Scale for 3 h post-dose and maximum change of Unified Parkinson's Disease Rating Scale part III for 3 h post-dose. Secondary objectives included effects on maximum Clinical Dyskinesia Rating Scale score, area under the curve of Rush Dyskinesia Rating Scale score for 3 h post-dose, mood parameters measured by Hospital Anxiety Depression Scale and Montgomery Asberg Depression Rating Scale along with the pharmacokinetics, safety and tolerability profile of eltoprazine. A mixed model repeated measures was used for post hoc analyses of the area under the curve and peak Clinical Dyskinesia Rating Scale scores. It was found that serum concentrations of eltoprazine increased in a dose-proportional manner. Following levodopa challenge, 5 mg eltoprazine caused a significant reduction of L-DOPA-induced dyskinesias on area under the curves of Clinical Dyskinesia Rating Scale [-1.02(1.49); P = 0.004] and Rush Dyskinesia Rating

  16. Drug Induced Hearing Loss: What Is Ototoxicity?

    MedlinePlus

    ... page please turn JavaScript on. Feature: Drug-Induced Hearing Loss What Is Ototoxicity? Past Issues / Spring 2016 Table ... of patients taking these drugs." "Antibiotics Caused My Hearing Loss..." Gulab Lalwani Photo Courtesy of: Gulab Lalwani When ...

  17. Cerebellar and Motor Cortical Transcranial Stimulation Decrease Levodopa-Induced Dyskinesias in Parkinson's Disease.

    PubMed

    Ferrucci, Roberta; Cortese, Francesca; Bianchi, Marta; Pittera, Dario; Turrone, Rosanna; Bocci, Tommaso; Borroni, Barbara; Vergari, Maurizio; Cogiamanian, Filippo; Ardolino, Gianluca; Di Fonzo, Alessio; Padovani, Alessandro; Priori, Alberto

    2016-02-01

    Transcranial direct current stimulation (tDCS) is a non-invasive technique for inducing prolonged functional changes in the human cerebral cortex. This simple and safe neurostimulation technique for modulating motor functions in Parkinson's disease could extend treatment option for patients with movement disorders. We assessed whether tDCS applied daily over the cerebellum (cerebellar tDCS) and motor cortex (M1-tDCS) improves motor and cognitive symptoms and levodopa-induced dyskinesias in patients with Parkinson's disease (PD). Nine patients (aged 60-85 years; four women; Hoehn & Yahr scale score 2-3) diagnosed as having idiopathic PD were recruited. To evaluate how tDCS (cerebellar tDCS or M1-tDCS) affects motor and cognitive function in PD, we delivered bilateral anodal (2 mA, 20 min, five consecutive days) and sham tDCS, in random order, in three separate experimental sessions held at least 1 month apart. In each session, as outcome variables, patients underwent the Unified Parkinson's Disease Rating Scale (UPDRS III and IV) and cognitive testing before treatment (baseline), when treatment ended on day 5 (T1), 1 week later (T2), and then 4 weeks later (T3), at the same time each day. After patients received anodal cerebellar tDCS and M1-tDCS for five days, the UPDRS IV (dyskinesias section) improved (p < 0.001). Conversely, sham tDCS, cerebellar tDCS, and M1-tDCS left the other variables studied unchanged (p > 0.05). Despite the small sample size, our preliminary results show that anodal tDCS applied for five consecutive days over the motor cortical areas and cerebellum improves parkinsonian patients' levodopa-induced dyskinesias. PMID:26542731

  18. Moclobemide-induced hypersexuality in patients with stroke and Parkinson's disease.

    PubMed

    Korpelainen, J T; Hiltunen, P; Myllylä, V V

    1998-01-01

    Decline in sexual activities caused by diseases or by medication affecting the functions of the central nervous system has often been described, but there are few reports on diseases or medications causing hypersexuality. Bilateral lesions of the temporal lobes may result in the Klüver-Bucy syndrome, symptoms of which include hypersexuality, excessive eating, and mood changes. In this article, the authors describe moclobemide-induced reversible hypersexuality, without other features of the Klüver-Bucy syndrome, in two patients with stroke and one patient with Parkinson's disease. PMID:9704167

  19. Environmental risk factors for Parkinson's disease and parkinsonism: the Geoparkinson study

    PubMed Central

    Dick, F D; De Palma, G; Ahmadi, A; Scott, N W; Prescott, G J; Bennett, J; Semple, S; Dick, S; Counsell, C; Mozzoni, P; Haites, N; Wettinger, S Bezzina; Mutti, A; Otelea, M; Seaton, A; Söderkvist, P; Felice, A

    2007-01-01

    Objective To investigate the associations between Parkinson's disease and other degenerative parkinsonian syndromes and environmental factors in five European countries. Methods A case–control study of 959 prevalent cases of parkinsonism (767 with Parkinson's disease) and 1989 controls in Scotland, Italy, Sweden, Romania and Malta was carried out. Cases were defined using the United Kingdom Parkinson's Disease Society Brain Bank criteria, and those with drug‐induced or vascular parkinsonism or dementia were excluded. Subjects completed an interviewer‐administered questionnaire about lifetime occupational and hobby exposure to solvents, pesticides, iron, copper and manganese. Lifetime and average annual exposures were estimated blind to disease status using a job‐exposure matrix modified by subjective exposure modelling. Results were analysed using multiple logistic regression, adjusting for age, sex, country, tobacco use, ever knocked unconscious and family history of Parkinson's disease. Results Adjusted logistic regression analyses showed significantly increased odds ratios for Parkinson's disease/parkinsonism with an exposure–response relationship for pesticides (low vs no exposure, odds ratio (OR) = 1.13, 95% CI 0.82 to 1.57, high vs no exposure, OR = 1.41, 95% CI 1.06 to 1.88) and ever knocked unconscious (once vs never, OR = 1.35, 95% CI 1.09 to 1.68, more than once vs never, OR = 2.53, 95% CI 1.78 to 3.59). Hypnotic, anxiolytic or antidepressant drug use for more than 1 year and a family history of Parkinson's disease showed significantly increased odds ratios. Tobacco use was protective (OR = 0.50, 95% CI 0.42 to 0.60). Analyses confined to subjects with Parkinson's disease gave similar results. Conclusions The association of pesticide exposure with Parkinson's disease suggests a causative role. Repeated traumatic loss of consciousness is associated with increased risk. PMID:17332139

  20. Soluble Epoxide Hydrolase Deficiency or Inhibition Attenuates MPTP-Induced Parkinsonism.

    PubMed

    Qin, Xiaocui; Wu, Qiaoqi; Lin, Lifang; Sun, Aimin; Liu, Shuhu; Li, Xiaowen; Cao, Xiong; Gao, Tianming; Luo, Pengcheng; Zhu, Xinhong; Wang, Xuemin

    2015-08-01

    Soluble epoxide hydrolase (sEH) inhibition has been demonstrated to have beneficial effects on various diseases, such as hypertension, diabetes, and brain ischemia. However, whether sEH inhibition has therapeutic potential in Parkinson's disease is still unknown. In this paper, we found that sEH expression is increased in 1-methyl-4-phenyl-1,2,3,6-tetrahydro pyridine (MPTP)-treated mice, and sEH deficiency and inhibition significantly attenuated tyrosine hydroxylase (TH)-positive cell loss and improved rotarod performance. The substrate of sEH, 14,15-epoxyeicosatrienoic acid (14,15-EET), protected TH-positive cells and alleviated the rotarod performance deficits of wild-type mice but not sEH-knockout mice. Moreover, the 14,15-EET antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE) abolished the neuronal protective effects of sEH deficiency. In primary cultured cortical neurons, MPP(+) induced significant Akt inactivation in neurons from sEH wild-type mice, and this effect was not observed in neurons from knockout mice. Our data indicate that sEH deficiency and inhibition increased 14,15-EET in MPTP-treated mice, which activated the Akt-mediated protection of TH-positive neurons and behavioral functioning. We also found that sEH deficiency attenuated TH-positive cell loss in a paraquat-induced mouse model of Parkinson's. Our data suggest that sEH inhibition might be a powerful tool to protect dopaminergic neurons in Parkinson's disease. PMID:25128026

  1. P300 in newly diagnosed non-dementing Parkinson's disease: effect of dopaminergic drugs.

    PubMed

    Prabhakar, S; Syal, P; Srivastava, T

    2000-09-01

    Changes in cognitive function are an integral part of the clinical presentation of Parkinson's Disease (PD). P300 potential studies in early stages of Parkinson's disease are lacking and effect of L-dopa therapy on these potentials is controversial. In this study, changes in P300 potentials in early stages of PD and effects of dopaminergic therapy were investigated. P300 waves were elicited by standard auditory 'odd ball' paradigm and were recorded before the start of therapy and 15 days, 3 and 6 months after the start of L-dopa therapy in 25 newly diagnosed patients with idiopathic PD. All patients were classified according to Hoehn and Yahr scale. Minimental status examination (MMSE) was done in all. Control group had 20 normal subjects. The P300 latency was not significantly increased in early Parkinson's disease. This latency was reduced with dopaminergic therapy on 15th day, but increased later. Implications of the data are discussed. PMID:11025627

  2. [Drug induced eosinophilic pleural effusion].

    PubMed

    Vasilescu, Raluca

    2014-01-01

    The hypersensitivity reactions induced by drugs, some widely used, like central nervous system medication, can have various presentations. The lung is a frequent target for such events. We present the case of 40-year-old male patient, non-smoker, with infant encephalopaty, seizures since age of 6 with polimorphic crisis (mainly absences), with anticonvulsivant treatment since 2011 (carbamazepine, sodium valproate, levetiracetam), with no respiratory medical history. Current symptoms started two weeks before, with chest pain, dry cough. He received no antibiotics. Chest X-ray and thoracic CT scan (27 June 2013) showed a left pleral effusion. Left exploratory thoracocentesis extracted 20 ml reddish pleural fluid: eosinophilic exsudate (60%) with normal adenosin deaminase. He also presents moderate blood eosinophilia (13.7%-1780/mm3). Pulmonary infarction with secondary pleurisy, thoracic trauma, acute pancreatitis with secondary pleurisy were excluded. No Loeffler transient infiltrates were documented, serology for Toxocara is IgG positive (historical) and not significant for current episode, no symptoms suggestive for toxocarosis (characteristic to young children, patient had no liver enlargement etc.), no hidatidosis or trichinelosis were found. As an exclusion diagnosis, a hypersensitivity reaction to anticonvulsivant medication was considered (mentioned in literature) carbamazepine and sodium valproate (even if medication was taken for a longer time), with blood and pleural eosinophilia. Together with the neurologist, the mentioned drugs were stopped and he was started on lamotrigine 2 tb/day and levetiracetam 1 tb/day, well tolerated, no absences were noticed. Total remission of blood eosinophilia and partial remission of pleural effusion were noticed. Subsequent follow-ups confirm favourable evolution, with healing of pleurisy and normal blood cell count, which are stable at 7 months after changing anticonvulsivant treatment. PMID:25241560

  3. Drug-induced hair colour changes.

    PubMed

    Bublin, J G; Thompson, D F

    1992-10-01

    Drug-induced hair colour changes are not a common adverse effect from medications. A wide variety of drugs have been implicated in causing hair colour changes but very few have data to support a true relationship. Of the drugs reported, chloroquine and cancer chemotherapeutic agents have the best evidence to support an association. Other drugs, such as p-aminobenzoic acid, calcium pantothenate, anthralin, chinoform, mephenesin, minoxidil, propofol, valproic acid, and verapamil await confirmatory data. Drug-induced causes should be considered in any patient with unexplained hair colour changes. PMID:1464633

  4. Drug-Induced Acute Pancreatitis: A Review

    PubMed Central

    Jones, Mark R.; Hall, Oliver Morgan; Kaye, Adam M.; Kaye, Alan David

    2015-01-01

    Background The majority of drug-induced pancreatitis cases are mild to moderate in severity, but severe and even fatal cases can occur. Management of drug-induced pancreatitis requires withdrawal of the offending agent and supportive care. Methods This review focuses on differential diagnosis, clinical presentation, drug-mediated effects, treatments, and mechanisms of pancreatitis, with an emphasis on drug-induced pancreatitis. Results Although only a minority of cases associated with acute pancreatitis are linked to drugs, clinical presentation and mechanisms of injury to the pancreas are not well understood by clinicians in terms of individual drug effects in the mediation or modulation of injury to the pancreas. In recent years, a large number of commonly prescribed medications has been linked to drug-induced pancreatitis pathogenesis. Although mechanisms are proposed, the exact cause of injury is either not well understood or controversial. Conclusion Future investigation into the mechanisms of pancreatitis and an appreciation by clinicians of the drugs commonly linked to the condition will help establish earlier diagnosis and quicker cessation of offending drugs in the treatment of drug-induced acute pancreatitis. PMID:25829880

  5. Viral Parkinsonism

    PubMed Central

    Jang, Haeman; Boltz, David A.; Webster, Robert G.; Smeyne, Richard Jay

    2015-01-01

    Parkinson's disease is a debilitating neurological disorder characterized that affects 1-2% of the adult population over 55 years of age. For the vast majority of cases, the etiology of this disorder is unknown, although it is generally accepted that there is a genetic susceptibility to any number of environmental agents. One such agent may be viruses. It has been shown that numerous viruses can enter the nervous system, i.e. they are neurotropic, and induce a number of encephalopathies. One of the secondary consequences of these encephalopathies can be parkinsonism, that is both transient as well as permanent. One of the most highlighted and controversial cases of viral parkinsonism is that which followed the 1918 influenza outbreak and the subsequent induction of von Economo's encephalopathy. In this review, we discuss the neurological sequelae of infection by influenza virus as well as that of other viruses known to induce parkinsonism including Coxsackie, Japanese encephalitis B, St. Louis, West Nile and HIV viruses. PMID:18760350

  6. Non-human primate FOG develops with advanced parkinsonism induced by MPTP Treatment

    PubMed Central

    Revuelta, Gonzalo J.; Uthayathas, Subramaniam; Wahlquist, Amy E.; Factor, Stewart A.; Papa, Stella M.

    2013-01-01

    Freezing of gait (FOG) is a debilitating feature of Parkinson’s disease (PD) and other forms of parkinsonism. The anatomical or pathophysiological correlates are poorly understood largely due to the lack of a well-established animal model. Here we studied whether FOG is reproduced in the non-human primate (NHP) model of PD. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys (Genus Macaca, n=29) were examined for the development of FOG, and the leg movements were recorded with accelerometry. The relationships between developing FOG and the animals’ characteristics, the MPTP treatments, and the modeled outcomes were determined. In parkinsonian monkeys FOG developed frequently (48%) manifesting similar characteristics to those seen in PD patients. In addition, FOG episodes in the monkey were accompanied by leg trembling with the typical duration (2–10 s) and frequency (~7 Hz). The development of NHP FOG was significantly associated with the severity of parkinsonism, as shown by high motor disability scores (≥20) and levodopa-induced dyskinesia scores (p=0.01 and p=0.04, respectively). Differences in demographics and MPTP treatments (doses, treatment duration, etc.) had no influence on NHP FOG occurrence, with the exception of gender that showed FOG predominance in males (p=0.03). The unique features of FOG in PD can be replicated in severely parkinsonian macaques, and this represents the first description of a FOG animal model. PMID:22967858

  7. Rotenone-induced energy stress decompensated in ventral mesocerebrum is associated with Parkinsonism progression in rats

    PubMed Central

    Bai, Qunhua; He, Junlin; Tang, Yong; Wang, Shibo; Qiu, Jingfu; Wang, Yang; Yu, Chao

    2016-01-01

    Parkinson's disease (PD) is the second most common neurodegenerative disorder, which is characterized by the hallmark feature of loss of dopaminergic neurons in the substantia nigra. Energy metabolic disorder is associated with the pathogenesis of PD; however, the development of this disorder is yet to be elucidated. PD-like characteristics have been demonstrated in a rotenone rat model. In the present study, energy metabolism status was investigated in a rat model following intraperitoneal treatment with 1.0 mg/kg rotenone every 48 h. The behavior and tyrosine hydroxylase-positive levels in the substantia nigra of rats that were treated with rotenone for 24 weeks demonstrated that these rats developed more severe parkinsonism, as compared with that were treated for 16 weeks. Detection of ATP, lactic acid, NADH dehydrogenase 1 mRNA and lactate dehydrogenase B mRNA levels in the ventral mesocerebrum (VM) and skeletal muscle (SM) of the rats that had been treated with rotenone for 16 and 24 weeks demonstrated that the energy stress induced by rotenone progressed in both VM and SM. Notably, the energy stress detected in VM was more severe, and this energy stress was decompensated in the VM of rats that had been treated with rotenone for 24 weeks. The progression of energy stress and the incidence of energy decompensation in VM may be important for the improvement of PD pathology. PMID:27446321

  8. Stepping test in mice: a reliable approach in determining forelimb akinesia in MPTP-induced Parkinsonism.

    PubMed

    Blume, Shannon R; Cass, Daryn K; Tseng, Kuei Y

    2009-09-01

    Currently existing behavioral measures for motor impairments in rodent models with bilateral dopamine depletion have demonstrated to be difficult to assess due to the degree of task complexity. There is clearly a need for a behavioral test that is simplistic in design and does not require the animal to learn a specific task, in particular for mice. Here we adapted the stepping test, originally designed for assessing asymmetric motor deficits in rats (Olsson, M., Nikkhah, G., Bentlage, C., Bjorklund, A., 1995. Forelimb akinesia in the rat Parkinson model: differential effects of dopamine agonists and nigral transplants as assessed by a new stepping test. J. Neurosci. 15, 3863-3875; Schallert, T., De Ryck, M., Whishaw, I.Q., Ramirez, V.D., Teitelbaum, P., 1979. Excessive bracing reactions and their control by atropine and l-DOPA in an animal analog of Parkinsonism. Exp. Neurol. 64, 33-43), into a mouse-friendly version for bilateral dopamine lesion induced by subacute MPTP injection. We found that MPTP-treated mice exhibit a significant and persistent reduction in the number of adjusting steps when compared to saline-treated animals. Typically, MPTP-induced stepping deficit becomes apparent by the fourth MPTP injection. The number of adjusting steps continues to decline throughout the injections, and by day 10 from the last MPTP injection, the stepping deficit observed is associated with approximately 65% TH positive cells loss in the SN. Importantly, L-DOPA administration significantly improved stepping performance in MPTP-treated mice. Thus, stepping test in mice is a reliable and simple behavioral measure for assessing forelimb akinesia induced by systemic MPTP. PMID:19460369

  9. Welding and parkinsonism.

    PubMed

    Furbee, Brent

    2011-08-01

    Manganese-induced parkinsonism has been recognized since 1837. It has been reported primarily in miners, grinders, and smelters since that time. More recently, isolated case reports involving welders have appeared in the medical literature. Manganism can be distinguished from other forms of parkinsonism by clinical presentation with support from laboratory and radiologic findings. The controversy regarding the risk of parkinsonism in welders is reviewed. PMID:21803214

  10. Dopamine improves exploration after expectancy violations and induces psychotic-like experiences in patients with Parkinson's disease.

    PubMed

    Polner, Bertalan; Moustafa, Ahmed A; Nagy, Helga; Takáts, Annamária; Győrfi, Orsolya; Kéri, Szabolcs

    2016-03-11

    Dopamine neurons are sensitive to novel and rewarding events, and dopamine signals can modulate learning in higher-level brain networks. Additionally, dopamine abnormalities appear to be central to the pathophysiology of schizophrenia spectrum disorders. In this study, we investigate the dopaminergic modulation of schizotypal traits and exploration after expectancy violations in Parkinson's disease (PD) patients on dopamine replacement therapy. Exploration after expectancy violations was measured with a latent inhibition and an anomaly categorisation task. Patients with PD had significantly elevated levels of schizotypy and reduced latent inhibition, relative to the controls. Anomaly categorisation was enhanced at trend level among the patients. Dopaminergic antiparkinsonian drugs showed dose-dependent effects: they induced psychotic-like experiences, and at the same time, they disrupted latent inhibition and made categorisation of anomaly more efficient. Most of these findings were replicated in an independent sample of patients with PD. An up-regulated dopamine system in medicated PD patients might tune higher-level brain networks to engage in learning when faced with unexpected information, and therefore hasten the updating of internal models. PMID:26820375

  11. Neuroprotective effects of ginkgetin against neuroinjury in Parkinson's disease model induced by MPTP via chelating iron.

    PubMed

    Wang, Y-Q; Wang, M-Y; Fu, X-R; Peng-Yu; Gao, G-F; Fan, Y-M; Duan, X-L; Zhao, B-L; Chang, Y-Z; Shi, Z-H

    2015-01-01

    Disruption of neuronal iron homeostasis and oxidative stress are closely related to the pathogenesis of Parkinson's disease (PD). Ginkgetin, a natural biflavonoid isolated from leaves of Ginkgo biloba L, has many known effects, including anti-inflammatory, anti-influenza virus, and anti-fungal activities, but its underlying mechanism of the neuroprotective effects in PD remains unclear. The present study utilized PD models induced by 1-methyl-4-phenylpyridinium (MPP(+)) and 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) to explore the neuroprotective ability of ginkgetin in vivo and in vitro. Our results showed that ginkgetin could provide significant protection from MPP(+)-induced cell damage in vitro by decreasing the levels of intracellular reactive oxygen species and maintaining mitochondrial membrane potential. Meanwhile, ginkgetin dramatically inhibited cell apoptosis induced by MPP+ through the caspase-3 and Bcl2/Bax pathway. Moreover, ginkgetin significantly improved sensorimotor coordination in a mouse PD model induced by MPTP by dramatically inhibiting the decrease of tyrosine hydroxylase expression in the substantia nigra and superoxide dismutase activity in the striatum. Interestingly, ginkgetin could strongly chelate ferrous ion and thereby inhibit the increase of the intracellular labile iron pool through downregulating L-ferritin and upregulating transferrin receptor 1. These results indicate that the neuroprotective mechanism of ginkgetin against neurological injury induced by MPTP occurs via regulating iron homeostasis. Therefore, ginkgetin may provide neuroprotective therapy for PD and iron metabolism disorder related diseases. PMID:25968939

  12. [Drug-induced acute kidney injury].

    PubMed

    Derungs, Adrian

    2015-12-01

    Due to their physiological function, the kidneys are exposed to high concentrations of numerous drugs and their metabolites, making them vulnerable to drug-related injuries. This article provides an overview of the pathophysiological mechanisms involved in nephrotoxicity, the most common nephrotoxic drugs, and the risk factors for the occurrence of drug-induced acute kidney injuries. NSAIDs, diuretics, ACE inhibitors, and angiotensin II receptor blockers (ARBs} are the most frequent prerenal causes of an acute elevation in creatinine levels. Primary vascular damage arises from thrombotic microangiopathy (e. g. due to cic/osporin, tacrolimus, muromonab-CD3, mitomycin C, quinine, ticlopidine, clopidogrel}. Anticoagulants and thrombolytic medications lead to secondary blood vessel damage by cholesterol emboli, embolism of thrombus material into the periphery or bleeding. Tubulopathies can be observed on treatment with ifosfamide and cisplatin (rarely with cyclophosphamide or carboplatin), aminoglycosides, vancomycin, and radiocontrast agents. Immunological mechanisms underlie interstitial nephritides, which are induced by drugs in about 85% of cases. In drug-induced glomerulopathies;- renal biopsy allows closer identification of the triggering medication. Drug-induced systemic lupus erythematosus (SLE} represents a special form of immune complex glomerulonephritis and can be triggered by procainamide, hydralazine, isoniazid, methyldopa, quinidine, chlorpromazine, and propylthiouracil. Crystal-induced kidney injury is caused by precipitation of drugs (e. g. aciclovir, sulfonamide antibiotics, methotrexate, indinavir) in the renal tubules and the urine-conducting organs with consecutive obstruction thereof. PMID:26654816

  13. Treatment of drug-induced seizures.

    PubMed

    Chen, Hsien-Yi; Albertson, Timothy E; Olson, Kent R

    2016-03-01

    Seizures are a common complication of drug intoxication, and up to 9% of status epilepticus cases are caused by a drug or poison. While the specific drugs associated with drug-induced seizures may vary by geography and change over time, common reported causes include antidepressants, stimulants and antihistamines. Seizures occur generally as a result of inadequate inhibitory influences (e.g., gamma aminobutyric acid, GABA) or excessive excitatory stimulation (e.g. glutamate) although many other neurotransmitters play a role. Most drug-induced seizures are self-limited. However, status epilepticus occurs in up to 10% of cases. Prolonged or recurrent seizures can lead to serious complications and require vigorous supportive care and anticonvulsant drugs. Benzodiazepines are generally accepted as the first line anticonvulsant therapy for drug-induced seizures. If benzodiazepines fail to halt seizures promptly, second line drugs include barbiturates and propofol. If isoniazid poisoning is a possibility, pyridoxine is given. Continuous infusion of one or more anticonvulsants may be required in refractory status epilepticus. There is no role for phenytoin in the treatment of drug-induced seizures. The potential role of ketamine and levetiracetam is promising but not established. PMID:26174744

  14. Non-steroidal drug-induced glaucoma

    PubMed Central

    Razeghinejad, M R; Pro, M J; Katz, L J

    2011-01-01

    Numerous systemically used drugs are involved in drug-induced glaucoma. Most reported cases of non-steroidal drug-induced glaucoma are closed-angle glaucoma (CAG). Indeed, many routinely used drugs that have sympathomimetic or parasympatholytic properties can cause pupillary block CAG in individuals with narrow iridocorneal angle. The resulting acute glaucoma occurs much more commonly unilaterally and only rarely bilaterally. CAG secondary to sulfa drugs is a bilateral non-pupillary block type and is due to forward movement of iris–lens diaphragm, which occurs in individuals with narrow or open iridocorneal angle. A few agents, including antineoplastics, may induce open-angle glaucoma. In conclusion, the majority of cases with glaucoma secondary to non-steroidal medications are of the pupillary block closed-angle type and preventable if the at-risk patients are recognized and treated prophylactically. PMID:21637303

  15. PACAP27 prevents Parkinson-like neuronal loss and motor deficits but not microglia activation induced by prostaglandin J2

    PubMed Central

    Shivers, Kai-Yvonne; Nikolopoulou, Anastasia; Machlovi, Saima Ishaq; Vallabhajosula, Shankar; Figueiredo-Pereira, Maria E.

    2014-01-01

    Neuroinflammation is a major risk factor in Parkinson disease (PD). Alternative approaches are needed to treat inflammation, as anti-inflammatory drugs such as NSAIDs that inhibit cyclooxygenase-2 (COX-2) can produce devastating side effects, including heart attack and stroke. New therapeutic strategies that target factors downstream of COX-2, such as prostaglandin J2 (PGJ2), hold tremendous promise because they will not alter the homeostatic balance offered by COX-2 derived prostanoids. In the current studies, we report that repeated microinfusion of PGJ2 into the substantia nigra of non-transgenic mice, induces three stages of pathology that mimic the slow-onset cellular and behavioral pathology of PD: mild (one injection) when only motor deficits are detectable, intermediate (two injections) when neuronal and motor deficits as well as microglia activation are detectable, and severe (four injections) when dopaminergic neuronal loss is massive accompanied by microglia activation and motor deficits. Microglia activation was evaluated in vivo by positron emission tomography (PET) with [11C](R)PK11195 to provide a regional estimation of brain inflammation. PACAP27 reduced dopaminergic neuronal loss and motor deficits induced by PGJ2, without preventing microglia activation. The latter could be problematic in that persistent microglia activation can exert long-term deleterious effects on neurons and behavior. In conclusion, this PGJ2-induced mouse model that mimics in part chronic inflammation, exhibits slow-onset PD-like pathology and is optimal for testing diagnostic tools such as PET, as well as therapies designed to target the integrated signaling across neurons and microglia, to fully benefit patients with PD. PMID:24970746

  16. PACAP27 prevents Parkinson-like neuronal loss and motor deficits but not microglia activation induced by prostaglandin J2.

    PubMed

    Shivers, Kai-Yvonne; Nikolopoulou, Anastasia; Machlovi, Saima Ishaq; Vallabhajosula, Shankar; Figueiredo-Pereira, Maria E

    2014-09-01

    Neuroinflammation is a major risk factor in Parkinson's disease (PD). Alternative approaches are needed to treat inflammation, as anti-inflammatory drugs such as NSAIDs that inhibit cyclooxygenase-2 (COX-2) can produce devastating side effects, including heart attack and stroke. New therapeutic strategies that target factors downstream of COX-2, such as prostaglandin J2 (PGJ2), hold tremendous promise because they will not alter the homeostatic balance offered by COX-2 derived prostanoids. In the current studies, we report that repeated microinfusion of PGJ2 into the substantia nigra of non-transgenic mice, induces three stages of pathology that mimic the slow-onset cellular and behavioral pathology of PD: mild (one injection) when only motor deficits are detectable, intermediate (two injections) when neuronal and motor deficits as well as microglia activation are detectable, and severe (four injections) when dopaminergic neuronal loss is massive accompanied by microglia activation and motor deficits. Microglia activation was evaluated in vivo by positron emission tomography (PET) with [(11)C](R)PK11195 to provide a regional estimation of brain inflammation. PACAP27 reduced dopaminergic neuronal loss and motor deficits induced by PGJ2, without preventing microglia activation. The latter could be problematic in that persistent microglia activation can exert long-term deleterious effects on neurons and behavior. In conclusion, this PGJ2-induced mouse model that mimics in part chronic inflammation, exhibits slow-onset PD-like pathology and is optimal for testing diagnostic tools such as PET, as well as therapies designed to target the integrated signaling across neurons and microglia, to fully benefit patients with PD. PMID:24970746

  17. Dopamine transporter scanning in the evaluation of patients with suspected Parkinsonism: a case-based user's guide.

    PubMed

    Rodriguez-Porcel, Federico; Jamali, Sheheryar; Duker, Andrew P; Espay, Alberto J

    2016-01-01

    Given the wide range of manifestations of parkinsonism and its mimics, the diagnosis may remain elusive or be misattributed in some patients. Dopamine transporter (DAT) single photon emission computed tomography (SPECT) (DaTscan), an imaging technique that probes the integrity of the presynaptic nigrostriatal system, can be useful in the evaluation of clinically complex parkinsonian disorders in the appropriate context and when adequately interpreted. Pearls and pitfalls in the use of DaTscan for the differential diagnosis of parkinsonisms are reviewed using a case-based format. While the DaTscan is no replacement for a careful neurological examination in ascertaining the likelihood of Parkinson disease or other parkinsonisms in most clinical scenarios, it can be useful in the assessment of disorders where an abducting resting tremor, a prominent postural tremor, or incongruent features are not sufficiently clear on exam to distinguish neurodegenerative parkinsonism from dystonia, drug-induced parkinsonism and functional (psychogenic) parkinsonism, respectively. PMID:26564057

  18. Peganum Harmala L. Extract Reduces Oxidative Stress and Improves Symptoms in 6-Hydroxydopamine-Induced Parkinson's Disease in Rats.

    PubMed

    Rezaei, Maryam; Nasri, Sima; Roughani, Mehrdad; Niknami, Zeinab; Ziai, Seyed Ali

    2016-01-01

    Parkinson's disease is one of the most common neurodegenerative disorders. There are many documents about the effects of oxidative stress in Parkinson's disease etiology. Angiotensin II activates NADPH dependent oxidases and causes superoxides formation. Peganum harmala L. extract, which has angiotensin converting enzyme (ACE) inhibitory effect, is considered to evaluate oxidative stress inhibition and Parkinson's disease improvement. Male rats weighting 200-250 g were divided into 5 groups: Control, Neurotoxin (injection of 6-hydroxydopamine into left hemisphere substantia nigra), Peganum harmala's seeds aqueous extract (10 mg/kg) and captopril (5 mg/kg). Peganum harmala and captopril were injected intraperitonealy -144, -120, -96, -72, -48, -24, -2, 4 and 24 h relative to 6-hydroxydopamine injection time. Muscle stiffness, apomorphine induced unilateral rotation, amount of brain's protein oxidation and lipid peroxidation, ACE activity and histology of substantia nigra were assayed in all groups. Peganum harmala improved Muscle stiffness and one-direction rotation behavior significantly. It also reduced brain's lipid and protein oxidation levels in neurotoxin-injected rats significantly. In Peganum harmala group compared to control group, brain's ACE activity was significantly inhibited. In histological study, Peganum harmala prevented degeneration of dopaminergic neurons, too. In conclusion, aqueous extract of Peganum harmala could prevent symptoms and reduced oxidative stress markers in rats with Parkinson's disease induced by 6-hydroxydopamine. PMID:27610168

  19. Azithromycin induced bullous fixed drug eruption

    PubMed Central

    Das, Anupam; Sancheti, Karan; Podder, Indrashis; Das, Nilay Kanti

    2016-01-01

    Fixed drug eruption (FDE) is a common type of drug eruption seen in skin clinics. It is characterized by solitary or multiple, round to oval erythematous patches with dusky red centers, some of which may progress to bulla formation. Bullous FDE may be caused by a number of drugs. We hereby describe a case of azithromycin-induced bullous FDE; to the best of our knowledge, this is the first such case being reported. PMID:26997729

  20. Phenotype Standardization for Drug Induced Kidney Disease

    PubMed Central

    Mehta, Ravindra L; Awdishu, Linda; Davenport, Andrew; Murray, Patrick; Macedo, Etienne; Cerda, Jorge; Chakaravarthi, Raj; Holden, Arthur; Goldstein, Stuart L.

    2015-01-01

    Drug induced kidney disease is a frequent cause of renal dysfunction; however, there are no standards to identify and characterize the spectrum of these disorders. We convened a panel of international, adult and pediatric, nephrologists and pharmacists to develop standardized phenotypes for drug induced kidney disease as part of the phenotype standardization project initiated by the International Serious Adverse Events Consortium. We propose four phenotypes of drug induced kidney disease based on clinical presentation: acute kidney injury, glomerular, tubular and nephrolithiasis, along with primary and secondary clinical criteria to support the phenotype definition, and a time course based on the KDIGO/AKIN definitions of acute kidney injury, acute kidney disease and chronic kidney disease. Establishing causality in drug induced kidney disease is challenging and requires knowledge of the biological plausibility for the specific drug, mechanism of injury, time course and assessment of competing risk factors. These phenotypes provide a consistent framework for clinicians, investigators, industry and regulatory agencies to evaluate drug nephrotoxicity across various settings. We believe that this is first step to recognizing drug induced kidney disease and developing strategies to prevent and manage this condition. PMID:25853333

  1. The discovery of drug-induced illness.

    PubMed

    Jick, H

    1977-03-01

    The increased use of drugs (and the concurrent increased risks of drug-induced illness) require definition of relevant research areas and strategy. For established marketed drugs, research needs depend on the magnitudes of risk of an illness from a drug and the base-line risk. With the drug risk high and the base-line risk low, the problem surfaces in premarketing studies or through the epidemic that develops after marketing. If the drug adds slightly to a high base-line risk, the effect is undetectable. When both risks are low, adverse effects can be discovered by chance, but systematic case-referent studies can speed discovery. If both risks are high, clinical trials and nonexperimental studies may be used. With both risks intermediate, systematic evaluations, especially case-referent studies are needed. Newly marketed drugs should be routinely evaluated through compulsory registration and follow-up study of the earliest users. PMID:834226

  2. Parkinson disease

    MedlinePlus

    American Parkinson Disease Association. Parkinson's Disease Handbook: A Guide for Patients and Their Families. Revised 2009. Available at: www.apdaparkinson.org/uploads/files/MP51919AmParkinsonHBK-vaU.pdf . Accessed September 15, ...

  3. [Drug-induced thyroid dysfunctions].

    PubMed

    Krysiak, Robert; Okopień, Bogusław

    2014-01-01

    latrogenic disorders are an important cause of morbidity, mortality, and admission to hospital in developed countries. Similarly to many other organs, the thyroid gland may be affected by various drugs, often used for the treatment of non-thyroid disorders. Drugs may affect thyroid function via different mechanisms, including thyroid hormone production, storage, secretion and metabolism offering numerous targets for drug interventions. Usually, the effect of pharmacotherapy is observed more frequently and is stronger in case of the presence of the concomitant disorder of this gland. An understanding of the proposed mechanisms of these drug interactions and their evaluation and differential diagnosis is helpful in the interpretation of the findings associated thyroid disorders and in establishing the correct treatment. The purpose of this article is to review the present state of knowledge on the influence of various drugs on the hypothalamic-pituitary-adrenal axis. We discuss pros and cons of the use of these agents in patients with concomitant thyroid disease and provide the reader with recommendations concerning the diagnosis and treatment of iatrogenic thyroid disorders. PMID:26030960

  4. Neuroprotection of pramipexole in UPS impairment induced animal model of Parkinson's disease.

    PubMed

    Li, Chao; Guo, Yuan; Xie, Wenjie; Li, Xingang; Janokovic, Joseph; Le, Weidong

    2010-10-01

    Pramipexole (PPX), a dopamine (DA) receptor D3 preferring agonist, has been used as monotherapy or adjunct therapy to treat Parkinson's disease (PD) for many years. Several in vitro and in vivo studies in neurotoxin-induced DA neuron injury models have reported that PPX may possess neuroprotective properties. The present study is to evaluate the neuroprotection of PPX in a sustained DA neuron degeneration model of PD induced by ubiquitin-proteasome system (UPS) impairment. Adult C57BL/6 mice were treated with PPX (low dose 0.1 mg/kg or high dose 0.5 mg/kg, i.p, twice a day) started 7 days before, and continued after microinjection of proteasome inhibitor lactacystin in the medial forebrain bundle for a total 4 weeks. Animal behavior observation, and pathological and biochemical assays were conducted to determine the neuroprotective effects of PPX. We report here that PPX treatment significantly improves rotarod performance, attenuates DA neuron loss and striatal DA reduction, and alleviates proteasomal inhibition and microglial activation in the substantia nigra of lactacystin-lesioned mice. PPX can increase the levels of brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor and induce an activation of autophagy. Furthermore, pretreatment with D3 receptor antagonist U99194 can significantly block the PPX-mediated neuroprotection. These results suggest that multiple molecular pathways may be attributed to the neuroprotective effects of PPX in the UPS impairment model of PD. PMID:20635141

  5. Intranigral administration of substance P receptor antagonist attenuated levodopa-induced dyskinesia in a rat model of Parkinson's disease.

    PubMed

    Yang, Xinxin; Zhao, Hui; Shi, Hongjuan; Wang, Xiaoying; Zhang, Shenyang; Zhang, Zunsheng; Zu, Jie; Zhang, Wei; Shen, Xia; Cui, Guiyun; Hua, Fang

    2015-09-01

    Levodopa (L-dopa) remains the most effective drug in the treatment of Parkinson's disease (PD). However, L-dopa-induced dyskinesia (LID) has hindered its use for PD patients. The mechanisms of LID are not fully understood. Substance P (SP) receptor antagonist has been shown to reduce parkinsonism in animal models of PD, and ameliorate LID in PD rats. But the concrete mechanism is not fully understood. To address this issue, we produced a rat model of PD using 6-hydroxydompamine (6-OHDA) injections, and valid PD rats were intranigrally administrated with different doses of SP receptor antagonist LY303870 (5 nmol/day, 10 nmol/day and 20 nmol/day) following L-dopa (6 mg/kg/day, i.p.) plus benserazide (12 mg/kg/day, i.p.) for 23 days. We found that nigral SP levels were increased on days 3, 7 and 14 and decreased on day 21 after 6-hydroxydompamine lesions. But nigral SP levels kept increasing after repeated L-dopa administration in PD rats. Intranigral administration of low and moderate LY303870 reduced abnormal involuntary movements (AIMs) while improving motor deficits in PD rats treated with L-dopa plus benserazide. Microdialysis revealed that LY303870 (10 nmol/day) treatment attenuated the increase of striatal dopamine and the reduction of γ-aminobutyric acid in ventromedial thalamus of PD rats primed with L-dopa. Additionally, LY303870 (10 nmol/day) treatment prior to L-dopa administration reduced the phosphorylated levels of dopamine- and cyclic adenosine monophosphate-regulated phosphoprotein of 32 kDa at Thr 34 and extracellular signal-regulated kinases 1/2 as well as the levels of activity-regulated cytoskeleton-associated protein and Penk in L-dopa-primed PD rats. Taken together, these data showed that low and moderate SP receptor antagonists LY303870 could ameliorate LID via neurokinin 1 receptor without affecting therapeutic effect of L-dopa. PMID:26001615

  6. Serotonin neuron transplants exacerbate L-DOPA-induced dyskinesias in a rat model of Parkinson's disease.

    PubMed

    Carlsson, Thomas; Carta, Manolo; Winkler, Christian; Björklund, Anders; Kirik, Deniz

    2007-07-25

    Clinical trials in patients with Parkinson's disease have shown that transplants of fetal mesencephalic dopamine neurons can form a new functional innervation of the host striatum, but the clinical benefits have been highly variable: some patients have shown substantial recovery in motor function, whereas others have shown no improvement and even a worsening in the 3,4-dihydroxyphenyl-L-alanine (L-DOPA)-induced dyskinetic side effects. Differences in the composition of the grafted cell preparation may contribute to these discrepancies. In particular, the number of serotonin neurons contained in the graft can vary greatly depending on the dissection of the fetal tissue. Importantly, serotonin neurons have the ability to store and release dopamine, formed from exogenously administered L-DOPA. Here, we have evaluated the effect of transplants containing serotonin neurons, or a mixture of dopamine and serotonin neurons, on L-DOPA-induced dyskinesias in 6-hydroxydopamine-lesioned animals. As expected, dopamine neuron-rich grafts induced functional recovery, accompanied by a 60% reduction in L-DOPA-induced dyskinesia that developed gradually over the first 10 weeks. Rats with serotonin-rich grafts with few dopamine neurons, in contrast, showed a progressive worsening of their L-DOPA-induced dyskinesias over time, and no functional improvement. The antidyskinetic effect of dopamine-rich grafts was independent of the number of serotonin neurons present. We conclude that serotonin neurons in the grafts are likely to have a detrimental effect on L-DOPA-induced dyskinesias in cases in which the grafts contain no or few dopamine neurons. PMID:17652591

  7. Contrasting gene expression patterns induced by levodopa and pramipexole treatments in the rat model of Parkinson's disease.

    PubMed

    Taravini, Irene R; Larramendy, Celia; Gomez, Gimena; Saborido, Mariano D; Spaans, Floor; Fresno, Cristóbal; González, Germán A; Fernández, Elmer; Murer, Mario G; Gershanik, Oscar S

    2016-02-01

    Whether the treatment of Parkinson's disease has to be initiated with levodopa or a D2 agonist like pramipexole remains debatable. Levodopa is more potent against symptoms than D2 agonists, but D2 agonists are less prone to induce motor complications and may have neuroprotective effects. Although regulation of plastic changes in striatal circuits may be the key to their different therapeutic potential, the gene expression patterns induced by de novo treatments with levodopa or D2 agonists are currently unknown. By studying the whole striatal transcriptome in a rodent model of early stage Parkinson's disease, we have identified the gene expression patterns underlying therapeutically comparable chronic treatments with levodopa or pramipexole. Despite the overall relatively small size of mRNA expression changes at the level of individual transcripts, our data show a robust and complete segregation of the transcript expression patterns induced by both treatments. Moreover, transcripts related to oxidative metabolism and mitochondrial function were enriched in levodopa-treated compared to vehicle-treated and pramipexole-treated animals, whereas transcripts related to olfactory transduction pathways were enriched in both treatment groups compared to vehicle-treated animals. Thus, our data reveal the plasticity of genetic striatal networks possibly contributing to the therapeutic effects of the most common initial treatments for Parkinson's disease, suggesting a role for oxidative stress in the long term complications induced by levodopa and identifying previously overlooked signaling cascades as potentially new therapeutic targets. PMID:25963416

  8. Clinical phenotype and risk of levodopa-induced dyskinesia in Parkinson's disease.

    PubMed

    Nicoletti, Alessandra; Mostile, Giovanni; Nicoletti, Giuseppe; Arabia, Gennarina; Iliceto, Giovanni; Lamberti, Paolo; Marconi, Roberto; Morgante, Letterio; Barone, Paolo; Quattrone, Aldo; Zappia, Mario

    2016-05-01

    It is unclear whether patients with different clinical phenotypes of Parkinson's disease (PD) differ in their risk of developing levodopa-induced dyskinesia. We evaluated the possible association between clinical phenotypes and risk of levodopa-induced dyskinesia in PD patients using a case-control design. The FRAGAMP study is a large Italian multicenter study. Patients affected by PD diagnosed according to the Gelb's criteria were enrolled and underwent a face-to-face interview. Clinical scales were used to evaluate motor and cognitive impairment. Presence of dyskinesia was assessed by the item 32 of the UPDRS section IV. On the basis of the most prominent motor symptoms at onset PD, patients were classified as tremor-dominant, akinetic-rigid, or mixed type. 485 PD patients (292 men; mean age 65.6 ± 9.8) were enrolled in the study of whom 128 (26.4 %) presented levodopa-induced dyskinesia. Of the 485 patients, 311 (64.1 %) were classified as tremor-dominant, 104 (21.4 %) as Akinetic-Rigid and 70 (14.4 %) as mixed type. Multivariate logistic regression analysis showed a significant negative association between tremor-dominant phenotype and levodopa-induced dyskinesia (adjusted OR 0.48; 95 % CI 0.23-1.00; p value 0.05). When analysis was stratified by age at onset a stronger negative association was found among the late onset (>50 years) PD patients (OR 0.28; 95 % CI 0.11-0.70; p value 0.007) while no association was found among patients with an early onset. Our findings support the hypothesis that the occurrence of resting tremor as an initial manifestation of PD may predict a lower probability of developing levodopa-induced dyskinesia. PMID:26964541

  9. Immunomodulatory and neuroprotective effects of ginsenoside Rg1 in the MPTP(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) -induced mouse model of Parkinson's disease.

    PubMed

    Zhou, Ting-ting; Zu, Guo; Wang, Xi; Zhang, Xiao-gang; Li, Shao; Liang, Zhan-hua; Zhao, Jie

    2015-12-01

    Ginsenoside Rg1, one of the biologically active ingredients of ginseng, has been considered to be a candidate neuroprotective drug. The objective of the study was to study the protective effects of Rg1 through the peripheral and central inflammation in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model. Rg1 treatment protected TH-positive cells in the SNpc region from MPTP toxicity measured with immunofluoresence. The protein expression levels of TH in the SNpc region of MPTP-induced mice following treatment with Rg1 were higher than MPTP-induced mice which were tested with Western blot. The ratio of CD3(+)CD4(+) to CD3(+)CD8(+) T cells and CD4(+)CD25(+)Foxp3(+) regulatory T cells in the blood increased in MPTP-induced mice following treatment with Rg1 which were detected by flow cytometry analysis. Moreover, Rg1 reduced the serum concentrations of proinflammatory cytokines TNF-α, IFN-γ, IL-1β and IL-6 which were tested with enzyme-linked immunosorbent assay (ELISA). In addition, Rg1 inhibited the activation of microglia and reduced the infiltration of CD3(+) T cells into the SNpc region which were measured by immunofluorescence. Our results indicated that Rg1 may represent a promising drug for the treatment of PD via the regulation of the peripheral and central inflammation. PMID:26548343

  10. Effective Treatment of Manganese-Induced Occupational Parkinsonism With p-Aminosalicylic Acid: A Case of 17-Year Follow-Up Study

    PubMed Central

    Jiang, Yue-Ming; Mo, Xue-An; Du, Feng-Qi; Fu, Xue; Zhu, Xia-Yan; Gao, Hong-Yu; Xie, Jin-Lan; Liao, Feng-Ling; Pira, Enrico; Zheng, Wei

    2014-01-01

    Objective Chronic manganese (Mn) intoxication induces syndromes resembling Parkinson disease. The clinical intervention has largely been unsuccessful. We report a 17-year follow-up study of effective treatment of occupational Mn parkinsonism with sodium para-aminosalicylic acid (PAS). Methods The patient, female and aged 50 at the time of treatment, was exposed to airborne Mn for 21 years (1963–1984). The patient had palpitations, hand tremor, lower limb myalgia, hypermyotonia, and a distinct festinating gait. She received 6 g PAS per day through an intravenous drip infusion for 4 days and rested for 3 days as one therapeutic course. Fifteen such courses were carried out between March and June 1987. Results At the end of PAS treatment, her symptoms were significantly alleviated, and handwriting recovered to normal. Recent follow-up examination at age 67 years (in 2004) showed a general normal presentation in clinical, neurologic, brain magnetic resonance imaging, and handwriting examinations with a minor yet passable gait. Conclusions This case study suggests that PAS appears to be an effective drug for treatment of severe chronic Mn poisoning with a promising prognosis. PMID:16766929

  11. A rare manifestation of atrial fibrillation in the presence of Wolff-Parkinson-White syndrome: tachycardia-induced cardiomyopathy.

    PubMed

    Değirmencioğu, Aleks; Karakuş, Gültekin; Baysal, Erkan; Zencirci, Ertuğrul; Çakmak, Nazmiye

    2014-03-01

    We report a 68-year-old man who presented with heart failure and atrial fibrillation (AF) with rapid ventricular response and wide QRS complexes. Tachycardia-induced cardiomyopathy (TIC) due to persistent AF developing on the basis of Wolff-Parkinson-White (WPW) syndrome was considered. Signs and symptoms of heart failure improved with restoration of sinus rhythm. This case suggested that persistent AF in a patient with WPW syndrome is one of the rare causes of TIC. PMID:24643151

  12. Naloxone reverses L-dopa induced overstimulation effects in a Parkinson's disease animal model analogue.

    PubMed

    Carey, R J

    1991-01-01

    Chronic L-DOPA treatment of Parkinson's disease frequently leads to the development of motoric overstimulation and hyperkinetic movements. To investigate this problem in the laboratory, rats surgically altered by unilateral 6-hydroxydopamine lesions (6-OHDA) were chronically treated with one L-DOPA (10 mg/kg i.p.) injection per day for 20 days. In this 6-OHDA rotation model, the unilateral dopamine denervation results in a profound contralateral sensory-motor neglect and the animals spontaneously rotate in a direction ipsilateral to the dopamine depleted hemisphere. Initially, the L-DOPA treatment did not alter the response bias but after several weeks, the response bias was reversed and the animals rotated in the formerly akinetic direction, contralaterally, at a significantly higher level. Using this overstimulation effect as an analogue of the clinically observed L-DOPA overstimulation, animals were given naloxone in conjunction with the L-DOPA treatment. Naloxone (0.10, 0.25 and 0.50 mg/kg i.p.) produced a dose related decrease in the L-DOPA induced contralateral rotation. Consistent with an expected selective effect on the L-DOPA induced rotation, a dose related increase in ipsilateral rotation was observed. These results suggest that naloxone can attenuate the overstimulation effect of L-DOPA and that this effect is not attributable to non-specific response suppression effects. PMID:1900558

  13. Neuromelanin activates microglia and induces degeneration of dopaminergic neurons: implications for progression of Parkinson's disease

    PubMed Central

    Zhang, Wei; Phillips, Kester; Wielgus, Albert R.; Liu, Jie; Albertini, Alberto; Zucca, Fabio A.; Faust, Rudolph; Qian, Steven Y.; Miller, David S.; Chignell, Colin F.; Wilson, Belinda; Jackson-Lewis, Vernice; Przedborski, Serge; Joset, Danielle; Loike, John; Hong, Jau-Shyong; Sulzer, David; Zecca, Luigi

    2013-01-01

    In Parkinson's disease (PD), there is a progressive loss of neuromelanin (NM)-containing dopamine (DA) neurons in substantia nigra (SN) which is associated with microgliosis and presence of extracellular NM. Herein, we have investigated the interplay between microglia and human NM on the degeneration of SN dopaminergic neurons. Although NM particles are phagocytised and degraded by microglia within minutes in vitro, extracellular NM particles induce microglial activation and ensuing production of superoxide, nitric oxide (NO), hydrogen peroxide (H2O2), and pro-inflammatory factors. Furthermore, NM produces, in a microglia-depended manner, neurodegeneration in primary ventral midbrain cultures. Neurodegeneration was effectively attenuated with microglia derived from mice deficient in macrophage antigen complex-1 (Mac-1), a microglial integrin receptor involved in the initiation of phagocytosis. Neuronal loss was also attenuated with microglia derived from mice deficient in phagocytic oxidase (PHOX), a subunit of NADPH oxidase, that is responsible for superoxide and H2O2 production, or apocyanin, a NADPH oxidase inhibitor. In vivo, NM injected into rat SN produces microgliosis and a loss of tyrosine hydroxylase (TH) neurons. Thus, these results show that extracellular NM can activate microglia, which in turn, may induce dopaminergic neurodegeneration in PD. Our study may have far-reaching implications, both pathogenic and therapeutic. PMID:19957214

  14. Foetal Cell Transplantation for Parkinson's Disease: Focus on Graft-Induced Dyskinesia

    PubMed Central

    Tronci, Elisabetta; Fidalgo, Camino; Carta, Manolo

    2015-01-01

    Transplantation of dopamine- (DA-) rich foetal ventral mesencephalic cells emerged as a promising therapy for Parkinson's disease (PD), as it allowed significant improvement of motor symptoms in several PD patients in open-label studies. However, double-blind clinical trials have been largely disappointing. The general agreement in the field is that the lack of standardization of tissue collection and preparation, together with the absence of postsurgical immunosuppression, played a key role in the failure of these studies. Moreover, a further complication that emerged in previous studies is the appearance of the so-called graft-induced dyskinesia (GID), in a subset of grafted patients, which resembles dyskinesia induced by L-DOPA but in the absence of medication. Preclinical evidence pointed to the serotonin neurons as possible players in the appearance of GID. In agreement, clinical investigations have shown that grafted tissue may contain a large number of serotonin neurons, in the order of half of the DA cells; moreover, the serotonin 5-HT1A receptor agonist buspirone has been found to produce significant dampening of GID in grafted patients. In this paper, we will review the recent preclinical and clinical studies focusing on cell transplantation for PD and on the mechanisms underlying GID. PMID:26881178

  15. Neurosteroid allopregnanolone attenuates cognitive dysfunctions in 6-OHDA-induced rat model of Parkinson's disease.

    PubMed

    Nezhadi, Akram; Sheibani, Vahid; Esmaeilpour, Khadijeh; Shabani, Mohammad; Esmaeili-Mahani, Saeed

    2016-05-15

    Cognitive deficits have an extensive influence on the quality of life of the Parkinson's disease (PD) patients. Previous studies have shown that lack of steroid hormones have an important role in the development of PD. Therefore, in this study the effects of neurosteroid allopregnanolone (Allo) on the PD-induced cognitive disorders were assessed. To simulate PD, 6-hydroxydopamine (6-OHDA) was injected into the rat's substantia nigra. Allo (5 and 20mg/kg, orally) were administered on the day after the 6-OHDA injection and continued during the entire treatment period (two months). Cognitive behaviors were assessed by Moris water maze (MWM), novel object recognition (NOR) and object location tasks. The data indicated that Allo significantly improved the 6-OHDA-induced cognitive impairment which revealed by the reduction of time spent to find out platform (escape latency) and the increase of retention time in MWM test and also with increase in the exploration index in NOR and object location tasks. Present study strongly supports the pro-cognitive property of allopregnanolone in PD. PMID:26970579

  16. BCG Vaccine-Induced Neuroprotection in a Mouse Model of Parkinson's Disease

    PubMed Central

    Yong, Jing; Lacan, Goran; Dang, Hoa; Hsieh, Terry; Middleton, Blake; Wasserfall, Clive; Tian, Jide; Melega, William P.; Kaufman, Daniel L.

    2011-01-01

    There is a growing interest in using vaccination with CNS antigens to induce autoreactive T cell responses that home to damaged areas in the CNS and ameliorate neurodegenerative disease. Neuroprotective vaccine studies have focused on administering oligodendrocyte antigens or Copaxone® in complete Freund's adjuvant (CFA). Theoretical considerations, however, suggest that vaccination with a neuronal antigen may induce more robust neuroprotective immune responses. We assessed the neuroprotective potential of vaccines containing tyrosine hydroxylase (a neuronal protein involved in dopamine synthesis) or Copaxone® in CFA in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. Surprisingly, we observed that the main beneficial factor in these vaccines was the CFA. Since the major immunogenic component in CFA is Mycobacterium tuberculosis, which closely related to the bacille Calmette-Guérin (BCG) that is used in human vaccines, we tested BCG vaccination in the MPTP mouse model. We observed that BCG vaccination partially preserved markers of striatal dopamine system integrity and prevented an increase in activated microglia in the substantia nigra of MPTP-treated mice. These results support a new neuroprotective vaccine paradigm in which general (nonself-reactive) immune stimulation in the periphery can limit potentially deleterious microglial responses to a neuronal insult and exert a neurorestorative effect in the CNS. Accordingly, BCG vaccination may provide a new strategy to augment current treatments for a wide range of neuropathological conditions. PMID:21304945

  17. BCG vaccine-induced neuroprotection in a mouse model of Parkinson's disease.

    PubMed

    Yong, Jing; Lacan, Goran; Dang, Hoa; Hsieh, Terry; Middleton, Blake; Wasserfall, Clive; Tian, Jide; Melega, William P; Kaufman, Daniel L

    2011-01-01

    There is a growing interest in using vaccination with CNS antigens to induce autoreactive T cell responses that home to damaged areas in the CNS and ameliorate neurodegenerative disease. Neuroprotective vaccine studies have focused on administering oligodendrocyte antigens or Copaxone® in complete Freund's adjuvant (CFA). Theoretical considerations, however, suggest that vaccination with a neuronal antigen may induce more robust neuroprotective immune responses. We assessed the neuroprotective potential of vaccines containing tyrosine hydroxylase (a neuronal protein involved in dopamine synthesis) or Copaxone® in CFA in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. Surprisingly, we observed that the main beneficial factor in these vaccines was the CFA. Since the major immunogenic component in CFA is Mycobacterium tuberculosis, which closely related to the bacille Calmette-Guérin (BCG) that is used in human vaccines, we tested BCG vaccination in the MPTP mouse model. We observed that BCG vaccination partially preserved markers of striatal dopamine system integrity and prevented an increase in activated microglia in the substantia nigra of MPTP-treated mice. These results support a new neuroprotective vaccine paradigm in which general (nonself-reactive) immune stimulation in the periphery can limit potentially deleterious microglial responses to a neuronal insult and exert a neurorestorative effect in the CNS. Accordingly, BCG vaccination may provide a new strategy to augment current treatments for a wide range of neuropathological conditions. PMID:21304945

  18. [Drug induced hemolytic anemia associated with agranulocytosis].

    PubMed

    Satoh, S; Takahashi, T; Hayashi, T; Okada, Y; Tokunoh, T; Adachi, M; Hinoda, Y; Endoh, T; Imai, K

    1996-10-01

    A 27-year-old female was admitted to a hospital because of severe anemia (hemoglobin 4.9 g/dl) after taking PL (a drug for common cold consisted of Salicylamide, Acetaminophen, Caffeine and Promethazine methylene di-salicylate) and Cefadroxil (an oral antibiotic) for ten days. History and laboratory data leaded to a diagnosis of drug induced hemolytic anemia. 6 units of concentrated red blood cells were transfused and the suspected drugs were discontinued immediately. Though resolution of anemia and no further hemolysis were observed, progressive leukocytopenia developed since four days after the admission. Bone marrow aspiration revealed marked decrease of granulocytic series. The patient was transferred to our hospital and was isolated under laminar air-flow to prevent her from bacterial and fungal infections. She was treated with prednisolone and granulocyte-colony stimulating factor. She recovered from leukocytopenia in two weeks without suffering from any life-threatening infection. We extensively analyzed the suspected drugs and mechanism of hemolysis and granulocytopenia. Cefadroxil is turned out to be contributed to hemolysis by an immune complex mechanism. Cefadroxil and Salicylamide were suggested to be involved in granulocytopenia by the induction of antibodies against the leukocytes to which these drugs were bound. Thus Cefadroxil was regarded as a causative drug of both hemolysis and granulocytopenia. This case is of interest for analyzing drug-induced blood abnormality because it is very rare that two lineage of blood were injured by one drug at the same time as far as we know. PMID:8952318

  19. Drug-Induced Oxidative Stress and Toxicity

    PubMed Central

    Deavall, Damian G.; Martin, Elizabeth A.; Horner, Judith M.; Roberts, Ruth

    2012-01-01

    Reactive oxygen species (ROS) are a byproduct of normal metabolism and have roles in cell signaling and homeostasis. Species include oxygen radicals and reactive nonradicals. Mechanisms exist that regulate cellular levels of ROS, as their reactive nature may otherwise cause damage to key cellular components including DNA, protein, and lipid. When the cellular antioxidant capacity is exceeded, oxidative stress can result. Pleiotropic deleterious effects of oxidative stress are observed in numerous disease states and are also implicated in a variety of drug-induced toxicities. In this paper, we examine the nature of ROS-induced damage on key cellular targets of oxidative stress. We also review evidence implicating ROS in clinically relevant, drug-related side effects including doxorubicin-induced cardiac damage, azidothymidine-induced myopathy, and cisplatin-induced ototoxicity. PMID:22919381

  20. Drug-Induced Dyskinesia, Part 1: Treatment of Levodopa-Induced Dyskinesia.

    PubMed

    Vijayakumar, Dhanya; Jankovic, Joseph

    2016-05-01

    Dyskinesias encompass a variety of different hyperkinetic phenomenologies, particularly chorea, dystonia, stereotypies, and akathisia. Levodopa-induced dyskinesia (LID) is one of the main types of drug-induced dyskinesia, occurring in patients with Parkinson's disease (PD) who have been treated with levodopa for long time, but this side effect may be encountered even within a few weeks or months after initiation of levodopa therapy. Based on the temporal pattern in relationship to levodopa dosing, LIDs are divided into "peak-dose dyskinesia," "diphasic dyskinesia," and "wearing off" or "off-period" dyskinesia, of which peak-dose dyskinesia is the most common, followed by off-period, and then diphasic dyskinesia. Treatment strategy includes identifying the kind of dyskinesia and tailoring treatment accordingly. Peak-dose dyskinesia is treated mainly by reducing individual doses of levodopa and adding amantadine and dopamine agonists, whereas off-period dystonia often responds to baclofen and botulinum toxin injections. Diphasic dyskinesias, occurring particularly in patients with young-onset PD, are the most difficult to treat. While fractionation of levodopa dosage is the most frequently utilized strategy, many patients require deep brain stimulation to control their troublesome motor fluctuations and LIDs. A variety of emerging (experimental) drugs currently in development promise to provide better control of LIDs and other levodopa-related complications in the near future. PMID:27091215

  1. Drug-induced arrhythmia: pharmacogenomic prescribing?

    PubMed Central

    Behr, Elijah R.; Roden, Dan

    2013-01-01

    Drug-induced Torsades de Pointes is a rare, unpredictable, and life-threatening serious adverse event. It can be caused by both cardiac and non-cardiac drugs and has become a major issue in novel drug development and for the regulatory authorities. This review describes the problem, predisposing factors, and the underlying genetic predisposition as it is understood currently. The future potential for pharmacogenomic-guided and personalized prescription to prevent drug-induced Torsades de Pointes is discussed. Database searches utilized reports from www.qtdrugs.org up to January 2012, case reports and articles from www.pubmed.com up to January 2012, and the British National Formulary edition at www.bnf.org. PMID:23091201

  2. Excessive daytime sleepiness in patients with Parkinson's disease.

    PubMed

    Knie, Bettina; Mitra, M Tanya; Logishetty, Kartik; Chaudhuri, K Ray

    2011-03-01

    Excessive daytime sleepiness (EDS) is described as inappropriate and undesirable sleepiness during waking hours and is a common non-motor symptom in Parkinson's disease, affecting up to 50% of patients. EDS has a large impact on the quality of life of Parkinson's disease patients as well as of their caregivers, in some cases even more than the motor symptoms of the disease. Drug-induced EDS is a particular problem as many dopamine agonists used for the treatment of Parkinson's disease have EDS as an adverse effect. Dopaminergic treatment may also render a subset of Parkinson's disease patients at risk for sudden-onset sleep attacks that occur without warning and can be particularly hazardous if the patient is driving. This demonstrates the need for early recognition and management not only to increase health-related quality of life but also to ensure patient safety. There are many assessment tools for EDS, including the Epworth Sleepiness Scale (ESS) and the Multiple Sleep Latency Test (MSLT), although only the Parkinson's Disease Sleep Scale (PDSS) and the SCales for Outcomes in PArkinson's Disease-Sleep (SCOPA-S) are specifically validated for Parkinson's disease. Polysomnography can be used when necessary. Management comprises non-pharmacological and pharmacological approaches. Non-pharmacological approaches can be the mainstay of treatment for mild to moderate EDS. Advice on good sleep hygiene is instrumental, as pharmacological approaches have yet to provide consistent and reliable results without significant adverse effects. The efficacy of pharmacological treatment of EDS in Parkinson's disease using wakefulness-promoting drugs such as modafinil remains controversial. Further areas of research are now also focusing on adenosine A(2A) receptor antagonists, sodium oxybate and caffeine to promote wakefulness. A definitive treatment for the highly prevalent drug-induced EDS has not yet been found. PMID:21323392

  3. Drug-induced immune neutropenia/agranulocytosis.

    PubMed

    Curtis, Brian R

    2014-01-01

    Neutrophils are the most abundant white blood cell in blood and play a critical role in preventing infections as part of the innate immune system. Reduction in neutrophils below an absolute count of 500 cells/pL is termed severe neutropenia or agranulocytosis. Drug-induced immune neutropenia (DIIN) occurs when drug-dependent antibodies form against neutrophil membrane glycoproteins and cause neutrophil destruction. Affected patients have fever, chills, and infections; severe infections left untreated can result in death. Treatment with granulocyte colony-stimulating factor can hasten neutrophil recovery. Cumulative data show that severe neutropenia or agranulocytosis associated with exposure to nonchemotherapy drugs ranges from approximately 1.6 to 15.4 cases per million population per year. Drugs most often associated with neutropenia or agranulocytosis include dipyrone, diclofenac, ticlopidine, calcium dobesilate, spironolactone, antithyroid drugs (e.g., propylthiouracil), carbamazepine, sulfamethoxazole- trimethoprim, [3-lactam antibiotics, clozapine, levamisole, and vancomycin. Assays used for detection of neutrophil drug-dependent antibodies (DDAbs) include flow cytometry, monoclonal antibody immobilization of granulocyte antigens, enzyme-linked immunosorbent assay, immunoblotting, granulocyte agglutination, and granulocytotoxicity. However, testing for neutrophil DDAbs is rarely performed owing to its complexity and lack of availability. Mechanisms proposed for DIIN have not been rigorously studied, but those that have been studied include drug- or hapten-induced antibody formation and autoantibody production against drug metabolite or protein adducts covalently attached to neutrophil membrane proteins. This review will address acute, severe neutropenia caused by neutrophil-reactive antibodies induced by nonchemotherapy drugs-DIIN PMID:25247619

  4. Drug-induced valvulopathy: an update.

    PubMed

    Elangbam, Chandikumar S

    2010-10-01

    Drug-induced valvulopathy is a serious liability for certain compound classes in development and for some marketed drugs intended for human use. Reports of valvulopathy led to the withdrawal of fenfluramines (anorexigens) and pergolide (antiparkinson drug) from the United States market in 1997 and 2007, respectively. The mechanism responsible for the pathogenesis of valvulopathy by these drugs is likely a result of an "off-target" effect via activation of 5-hydroxytryptamine (5-HT) 2B receptor (5-HT2BR) expressed on heart valve leaflets. Microscopically, the affected valve leaflets showed plaques of proliferative myofibroblasts in an abundant extracellular matrix, composed primarily of glycosaminoglycans. However, the valvular effects caused by fenfluramines and pergolide were not initially predicted from routine preclinical toxicity studies, and to date there are no specific validated animal models or preclinical/toxicologic screens to accurately predict drug-induced valvulopathy. This review covers the structure and function of heart valves and highlights major advances toward understanding the 5-HT2BR-mediated pathogenesis of the lesion and subsequently, development of appropriate animal models using novel techniques/experiments, use of functional screens against 5-HT2BR, and more consistent sampling and pathologic evaluation of valves in preclinical studies that will aid in avoidance of future drug-induced valvulopathy in humans. PMID:20716786

  5. Drug-Induced Nephrotoxicity and Its Biomarkers

    PubMed Central

    Kim, Sun Young; Moon, Aree

    2012-01-01

    Nephrotoxicity occurs when kidney-specific detoxification and excretion do not work properly due to the damage or destruction of kidney function by exogenous or endogenous toxicants. Exposure to drugs often results in toxicity in kidney which represents the major control system maintaining homeostasis of body and thus is especially susceptible to xenobiotics. Understanding the toxic mechanisms for nephrotoxicity provides useful information on the development of drugs with therapeutic benefi ts with reduced side effects. Mechanisms for drug-induced nephrotoxicity include changes in glomerular hemodynamics, tubular cell toxicity, inflammation, crystal nephropathy, rhabdomyolysis, and thrombotic microangiopathy. Biomarkers have been identifi ed for the assessment of nephrotoxicity. The discovery and development of novel biomarkers that can diagnose kidney damage earlier and more accurately are needed for effective prevention of drug-induced nephrotoxicity. Although some of them fail to confer specificity and sensitivity, several promising candidates of biomarkers were recently proved for assessment of nephrotoxicity. In this review, we summarize mechanisms of drug-induced nephrotoxicity and present the list of drugs that cause nephrotoxicity and biomarkers that can be used for early assessment of nephrotoxicity. PMID:24130922

  6. Drug-Induced Long QT Syndrome

    PubMed Central

    Kannankeril, Prince; Darbar, Dawood

    2010-01-01

    The drug-induced long QT syndrome is a distinct clinical entity that has evolved from an electrophysiologic curiosity to a centerpiece in drug regulation and development. This evolution reflects an increasing recognition that a rare adverse drug effect can profoundly upset the balance between benefit and risk that goes into the prescription of a drug by an individual practitioner as well as the approval of a new drug entity by a regulatory agency. This review will outline how defining the central mechanism, block of the cardiac delayed-rectifier potassium current IKr, has contributed to defining risk in patients and in populations. Models for studying risk, and understanding the way in which clinical risk factors modulate cardiac repolarization at the molecular level are discussed. Finally, the role of genetic variants in modulating risk is described. PMID:21079043

  7. Pharmacodynamics of drug-induced weight gain.

    PubMed

    Kulkarni, S. K.; Kaur, Gurpreet

    2001-08-01

    Body weight gain during treatment with drugs for any kind of disease may represent improvement of the disease itself. However, sometimes these drug-induced alterations of the body's appetite-regulating mechanisms result in excessive weight gain, thus jeopardizing compliance with prescribed medication. A number of drugs are capable of changing body weight as an adverse consequence of their therapeutic effect. Included in this category are the psychotropic drugs such as antipsychotics, antidepressants and mood stabilizers. Antipsychotics are well-known culprits of weight gain. The low-potency (e.g., chlorpromazine and thioridazine) and atypical agents (e.g., clozapine, olanzapine, quetiapine and risperidone) are most often associated with weight gain. Antidepressants such as tricyclic antidepressants and monoamine oxidase (MAO) inhibitors are most often associated with significant weight gain. The tertiary tricyclic antidepressant amitriptyline is thought to induce the most weight gain. Mood stabilizers such as lithium carbonate, valproic acid and carbamazepine also induce weight gain in a considerable number of patients. Treatment with corticosteroids is associated with dose-dependent body weight gain in many patients and corticosteroid-induced obesity aggravates other corticosteroid-associated health risks. Insulin therapy in diabetic patients usually increases body weight. Finally, sulfonylurea derivatives, antineoplastic agents used for the treatment of breast cancer and several drugs used in migraine prophylaxis may cause body weight gain as well. (c) 2001 Prous Science. All rights reserved. PMID:12743638

  8. Pustular psoriasis and drug-induced pustulosis.

    PubMed

    Serra, D; Gonçalo, M; Mariano, A; Figueiredo, A

    2011-04-01

    We report the case of a 65-year-old female patient that has suffered several flares of exanthematous pustulosis, some of them attributable to pustular psoriasis and others that were drug-induced, resembling acute generalized exanthematous pustulosis. In particular, we describe two severe flares that were induced by ciprofloxacin. Patch tests yielded positive results to ciprofloxacin and to other quinolones and reproduced the original lesional pattern both clinically and histologically. We discuss the diagnostic challenge that exanthematous pustulosis represents and the value of patch testing in this setting, as a helpful tool to assess drug participation in these eruptions. PMID:21505400

  9. SIRT3 Acts as a Neuroprotective Agent in Rotenone-Induced Parkinson Cell Model.

    PubMed

    Zhang, Jing-Yi; Deng, Yong-Ning; Zhang, Meng; Su, Hua; Qu, Qiu-Min

    2016-07-01

    SIRT3 is a member of Sirtuins family, which belongs to NAD(+) dependent class III histone deacetylases. Emerging evidence suggests that SIRT3 plays a pivotal role in regulating mitochondrial function. Mitochondrial dysfunction is a main pathogenesis of Parkinson's disease (PD). Here, we have investigated the protective effect of SIRT3 for PD cell model. The rotenone-induced human neuroblastoma SH-SY5Y cells damage was used as PD cell model. The lentiviral vectors were used to over-expression or knockdown SIRT3 expression. The cell viability was analyzed using MTT method. The apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were measured by flow cytometer. Superoxide dismutase (SOD) and glutathione (GSH) were detected by using automated microplate reader. The accumulation of α-synuclein was determined by immunofluorescence staining. SIRT3 knockdown significantly worsen rotenone-induced decline of cell viability (p < 0.01) and enhanced cell apoptosis (p < 0.01), exacerbated the decrease of SOD (p < 0.05) and GSH (p < 0.05), and augmented the accumulation of α-synuclein (p < 0.05). While SIRT3 overexpression dramatically increased cell viability (p < 0.01), and decreased cell apoptosis (p < 0.01), prevented the accumulation of α-synuclein (p < 0.05), suppressed the reducing of SOD (p < 0.05) and GSH (p < 0.01), decreased ROS generation (p < 0.05), and alleviated MMP collapse (p < 0.01) induced by rotenone. SIRT3 has neuroprotective effect in PD cell model and could be developed into a therapeutic agent for PD patients. PMID:27053302

  10. Palmitoyl Serotonin Inhibits L-dopa-induced Abnormal Involuntary Movements in the Mouse Parkinson Model.

    PubMed

    Park, Hye-Yeon; Ryu, Young-Kyoung; Go, Jun; Son, Eunjung; Kim, Kyoung-Shim; Kim, Mee Ree

    2016-08-01

    L-3,4-dihydroxyphenylalanine (L-DOPA) is the most common treatment for patients with Parkinson's disease (PD). However, long term use of L-DOPA for PD therapy lead to abnormal involuntary movements (AIMs) known as dyskinesia. Fatty acid amide hydrolase (FAAH) is enriched protein in basal ganglia, and inhibition of the protein reduces dyskinetic behavior of mice. Palmitoyl serotonin (PA-5HT) is a hybrid molecule patterned after arachidonoyl serotonin, antagonist of FAAH. However, the effect of PA-5HT on L-DOPA-induced dyskinesia (LID) in PD have not yet been elucidated. To investigate whether PA-5HT relieve LID in PD and decrease hyperactivation of dopamine D1 receptors, we used the 6-hydroxydopomine (6-OHDA)-lesioned mouse model of PD and treated the L-DOPA (20 mg/kg) for 10 days with PA-5HT (0.3 mg/kg/day). The number of wall contacts with the forelimb in the cylinder test was significantly decreased by 6-OHDA lesion in mice and the pharmacotherapeutic effect of L-DOPA was also revealed in PA-5HT-treated mice. Moreover, in AIMs test, PA-5HT-treated mice showed significant reduction of locomotive, axial, limb, and orofacial AIMs score compared to the vehicle-treated mice. LID-induced hyper-phosphorylation of ERK1/2 and overexpression of FosB/ΔFosB was markedly decreased in 6-OHDA-lesioned striatum of PA-5HT-treated mice, indicating that PA-5HT decreased the dopamine D1 receptor-hyperactivation induced by chronic treatment of L-DOPA in dopamine-denervated striatum. These results suggest that PA-5HT effectively attenuates the development of LID and enhance of ERK1/2 phosphorylation and FosB/ΔFosB expression in the hemi-parkinsonian mouse model. PA-5HT may have beneficial effect on the LID in PD. PMID:27574484

  11. Palmitoyl Serotonin Inhibits L-dopa-induced Abnormal Involuntary Movements in the Mouse Parkinson Model

    PubMed Central

    Park, Hye-Yeon; Ryu, Young-Kyoung; Go, Jun; Son, Eunjung

    2016-01-01

    L-3,4-dihydroxyphenylalanine (L-DOPA) is the most common treatment for patients with Parkinson's disease (PD). However, long term use of L-DOPA for PD therapy lead to abnormal involuntary movements (AIMs) known as dyskinesia. Fatty acid amide hydrolase (FAAH) is enriched protein in basal ganglia, and inhibition of the protein reduces dyskinetic behavior of mice. Palmitoyl serotonin (PA-5HT) is a hybrid molecule patterned after arachidonoyl serotonin, antagonist of FAAH. However, the effect of PA-5HT on L-DOPA-induced dyskinesia (LID) in PD have not yet been elucidated. To investigate whether PA-5HT relieve LID in PD and decrease hyperactivation of dopamine D1 receptors, we used the 6-hydroxydopomine (6-OHDA)-lesioned mouse model of PD and treated the L-DOPA (20 mg/kg) for 10 days with PA-5HT (0.3 mg/kg/day). The number of wall contacts with the forelimb in the cylinder test was significantly decreased by 6-OHDA lesion in mice and the pharmacotherapeutic effect of L-DOPA was also revealed in PA-5HT-treated mice. Moreover, in AIMs test, PA-5HT-treated mice showed significant reduction of locomotive, axial, limb, and orofacial AIMs score compared to the vehicle-treated mice. LID-induced hyper-phosphorylation of ERK1/2 and overexpression of FosB/ΔFosB was markedly decreased in 6-OHDA-lesioned striatum of PA-5HT-treated mice, indicating that PA-5HT decreased the dopamine D1 receptor-hyperactivation induced by chronic treatment of L-DOPA in dopamine-denervated striatum. These results suggest that PA-5HT effectively attenuates the development of LID and enhance of ERK1/2 phosphorylation and FosB/ΔFosB expression in the hemi-parkinsonian mouse model. PA-5HT may have beneficial effect on the LID in PD. PMID:27574484

  12. Milestones in Parkinson's disease therapeutics.

    PubMed

    Rascol, Olivier; Lozano, Andres; Stern, Matthew; Poewe, Werner

    2011-05-01

    In the mid-1980s, the treatment of Parkinson's disease was quite exclusively centered on dopatherapy and was focusing on dopamine systems and motor symptoms. A few dopamine agonists and a monoamine oxidase B inhibitor (selegiline) were used as adjuncts in advanced Parkinson's disease. In the early 2010s, levodopa remains the gold standard. New insights into the organization of the basal ganglia paved the way for deep brain stimulation, especially of the subthalamic nucleus, providing spectacular improvement of drug-refractory levodopa-induced motor complications. Novel dopamine agonists (pramipexole, ropinirole, rotigotine), catecholmethyltransferase inhibitors (entacapone), and monoamine oxidase B inhibitors (rasagiline) have also been developed to provide more continuous oral delivery of dopaminergic stimulation in order to improve motor outcomes. Using dopamine agonists early, before levodopa, proved to delay the onset of dyskinesia, although this is achieved at the price of potentially disabling daytime somnolence or impulse control disorders. The demonstration of an antidyskinetic effect of the glutamate antagonist amantadine opened the door for novel nondopaminergic approaches of Parkinson's disease therapy. More recently, nonmotor symptoms (depression, dementia, and psychosis) have been the focus of the first randomized controlled trials in this field. Despite therapeutic advances, Parkinson's disease continues to be a relentlessly progressive disorder leading to severe disability. Neuroprotective interventions able to modify the progression of Parkinson's disease have stood out as a failed therapeutic goal over the last 2 decades, despite potentially encouraging results with compounds like rasagiline. Newer molecular targets, new animal models, novel clinical trial designs, and biomarkers to assess disease modification have created hope for future therapeutic interventions. PMID:21626552

  13. Drug-induced neurotoxicity in addiction medicine: From prevention to harm reduction.

    PubMed

    Mohammad Ahmadi Soleimani, S; Ekhtiari, Hamed; Cadet, Jean Lud

    2016-01-01

    Neurotoxicity is considered as a major cause of neurodegenerative disorders. Most drugs of abuse have nonnegligible neurotoxic effects many of which are primarily mediated by several dopaminergic and glutamatergic neurotransmitter systems. Although many researchers have investigated the medical and cognitive consequences of drug abuse, the neurotoxicity induced by these drugs still requires comprehensive attention. The science of neurotoxicity promises to improve preventive and therapeutic strategies for brain disorders such as Alzheimer disease and Parkinson's disease. However, its clinical applications for addiction medicine remain to be defined adequately. This chapter reviews the most commonly discussed mechanisms underlying neurotoxicity induced by common drugs of abuse including amphetamines, cocaine, opiates, and alcohol. In addition, the known factors that trigger and/or predispose to drug-induced neurotoxicity are discussed. These factors include drug-related, individual-related, and environmental insults. Moreover, we introduce some of the potential pharmacological antineurotoxic interventions deduced from experimental animal studies. These interventions involve various targets such as dopaminergic system, mitochondria, cell death signaling, and NMDA receptors, among others. We conclude the chapter with a discussion of addicted patients who might benefit from such interventions. PMID:26806769

  14. Biomarkers of cell damage induced by oxidative stress in Parkinson's disease and related models.

    PubMed

    Tobón-Velasco, Julio César; Carmona-Aparicio, Liliana; Ali, Syed F; Santamaría, Abel

    2010-12-01

    One of the common features occurring in several experimental models of neurodegenerative disorders is oxidative/nitrosative stress (OS/NS). This event induces a series of deleterious actions involving the primary formation of reactive oxygen and nitrogen species (ROS/RNS), affecting both the structure and function of different biological molecules, and leading to specific toxic processes that compromise cell redox status. Biomarkers are important indicators of normal and abnormal biological processes. Specific biochemical and genetic changes observed in different pathologies bring us comprehensive information regarding the nature of any particular disorder. Parkinson's disease (PD) is a chronic neurodegenerative disorder difficult to study, given the intricate events occurring in the pathology, and also because the resultant clinical phenotype fluctuates over time. At present, we have no definitive diagnostic test, and thus for clinicians there is still expectation that biomarkers will eventually help to diagnose symptomatic and presymptomatic disease, or provide surrogated end-points to demonstrate clinical efficacy of new treatments and neuroprotective therapies. In this review we explore current information on some potential biomarkers of OS/NS in PD models, with special emphasis on the most-recent findings on this topic. PMID:20868359

  15. Neuroprotective role of Withania somnifera root extract in maneb-paraquat induced mouse model of parkinsonism.

    PubMed

    Prakash, Jay; Yadav, Satyndra Kumar; Chouhan, Shikha; Singh, Surya Pratap

    2013-05-01

    Parkinson's disease (PD) is a neurodegenerative disorder and these days a lot of emphasis is given on the treatment of this disease using herbal medicines. The present study evaluates the neuroprotective effect of Withania somnifera (Ws) root extract on Parkinsonian mice. The mice were divided into three groups; the first group served as control, the second group was given maneb (MB) and paraquat (PQ) and the last group was administered MB-PQ along with Ws root extract for 3, 6 and 9 weeks. The behavioral studies showed a significant improvement in the motor movement patterns and gripping ability of Ws root extract exposed Parkinsonian mice. Tyrosine hydroxylase (TH) immunostaining was reduced in the substantia nigra of MB-PQ exposed mice, while Ws co-exposure restored TH immunostaining significantly. Additionally, our results also demonstrate generation of oxidative stress in the nigrostriatal region of MB-PQ exposed mice. There was a marked decline in the level of catalase and a simultaneous increase in the level of nitrite and lipid peroxidation in Parkinsonian mice. Thus, the Ws root extract have shown to counteract the pro-oxidants and their associated oxidative stress in the PD model studied here. Our results clearly indicate the usefulness of Ws root extract in providing protection against MB-PQ induced nigrostriatal dopaminergic neurodegeneration and marked improvement in the behavioral, anatomical and the biochemical deformities. PMID:23430469

  16. Citalopram-induced hyponatraemia and parkinsonism: potentially fatal side-effects not to be missed.

    PubMed

    Damali Amiri, Negin; Wijenaike, Nishan

    2014-01-01

    The use of selective serotonin reuptake inhibitors (SSRIs), such as citalopram, is on the rise and, as such, clinicians must be vigilant of rare side-effects associated with this group of medications. We report the case of a 65-year-old man who presented to West Suffolk Hospital with a fall, confusion and movement abnormalities, and was found to have a serum sodium of 105 on admission. He was managed with hypertonic saline, dopamine agonists and intensive physiotherapy. Despite initially deteriorating neurologically, he made a remarkable recovery, and was discharged home at his pre-admission baseline. The learning points from this report are as follows: (1) regular monitoring of electrolytes on starting an SSRI (and similarly selective noradrenaline reuptake inhibitors-SNRIs) in SSRI/SNRIs naïve patients, (2) awareness of possible citalopram-induced parkinsonism and the potential benefits of dopamine agonists as one management strategy and (3) vigilant fluid/electrolyte monitoring in patients with profound hyponatraemia. PMID:25391825

  17. The Pael-R gene does not mediate the changes in rotenone-induced Parkinson's disease model cells

    PubMed Central

    Zou, Ting; Tang, Xiangqi; Huang, Zhiling; Xu, Niangui; Hu, Zhiping

    2014-01-01

    In this study, we established cell models for Parkinson's disease using rotenone. An RNA interference vector targeting Parkin-associated endothelin receptor-like receptor (Pael-R) was transfected into the model cells. The results of reverse-transcription polymerase chain reaction and western blot analysis showed that Pael-R expression was decreased after RNA interference compared with the control group (no treatment) and the model group (rotenone treatment), while the rate of apoptosis and survival of dopaminergic cells did not differ significantly between groups, as detected by flow cytometry and an MTT assay. These experimental findings indicate that the Pael-R gene has no role in the changes in rotenone-induced Parkinson's disease model cells. PMID:25206827

  18. Sigma-1 receptor deficiency reduces MPTP-induced parkinsonism and death of dopaminergic neurons

    PubMed Central

    Hong, J; Sha, S; Zhou, L; Wang, C; Yin, J; Chen, L

    2015-01-01

    Sigma-1 receptor (σ1R) has been reported to be decreased in nigrostriatal motor system of Parkinson's disease patients. Using heterozygous and homozygous σ1R knockout (σ1R+/− and σ1R−/−) mice, we investigated the influence of σ1R deficiency on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-impaired nigrostriatal motor system. The injection of MPTP for 5 weeks in wild-type mice (MPTP-WT mice), but not in σ1R+/− or σ1R−/− mice (MPTP-σ1R+/− or MPTP-σ1R−/− mice), caused motor deficits and ~40% death of dopaminergic neurons in substantia nigra pars compacta with an elevation of N-methyl-d-aspartate receptor (NMDAr) NR2B phosphorylation. The σ1R antagonist NE100 or the NR2B inhibitor Ro25-6981 could alleviate the motor deficits and the death of dopaminergic neurons in MPTP-WT mice. By contrast, MPTP-σ1R+/− mice treated with the σ1R agonist PRE084 or MPTP-σ1R−/− mice treated with the NMDAr agonist NMDA appeared to have similar motor deficits and loss of dopaminergic neurons as MPTP-WT mice. The pharmacological or genetic inactivation of σ1R suppressed the expression of dopamine transporter (DAT) in substantia nigra, which was corrected by NMDA. The activation of σ1R by PRE084 enhanced the DAT expression in WT mice or σ1R+/− mice. By contrast, the level of vesicular monoamine transporter 2 (VMAT2) in σ1R+/− mice or σ1R−/− mice had no difference from WT mice. Interestingly, MPTP-WT mice showed the reduction in the levels of DAT and VMAT2, but MPTP-σ1R−/− mice did not. The inactivation of σ1R by NE100 could prevent the reduction of VMAT2 in MPTP-WT mice. In addition, the activation of microglia cells in substantia nigra was equally enhanced in MPTP-WT mice and MPTP-σ1R−/− mice. The number of activated astrocytes in MPTP-σ1R−/− mice was less than that in MPTP-WT mice. The findings indicate that the σ1R deficiency through suppressing NMDAr function and DAT expression can reduce MPTP-induced death of

  19. [Drug-induced dystonia misinterpreted as hysteria].

    PubMed

    Magnusson, A; Opjordsmoen, S; Dietrichs, E

    1996-03-10

    Psychic distress is often expressed in the form of physical pain or disease, but the converse also occurs. Illnesses with an organic aetiology are sometimes misdiagnosed as psychogenic. We describe three patients who developed rare forms of acute drug-induced dystonia when treated with antipsychotic drugs. All three cases were initially misdiagnosed as "hysteria" because the patients had psychiatric illnesses and because the symptoms were bizarre and became worse when the patients became very anxious. Furthermore, if the patients were helped to relax the symptoms disappeared for a moment. One of the patients developed dystonia 24 hours after ingestion of 750 mg tetrabenazine in an attempt at suicide. Another patient who had HIV/AIDS developed severe dystonia after receiving only 2 mg haloperidol by mouth. The clinical presentation, treatment, and possible mechanisms of the pathophysiology of acute drug-induced dystonia are briefly reviewed. PMID:8644096

  20. microRNA-155 Regulates Alpha-Synuclein-Induced Inflammatory Responses in Models of Parkinson Disease.

    PubMed

    Thome, Aaron D; Harms, Ashley S; Volpicelli-Daley, Laura A; Standaert, David G

    2016-02-24

    Increasing evidence points to inflammation as a chief mediator of Parkinson's disease (PD), a progressive neurodegenerative disorder characterized by loss of dopamine neurons in the substantia nigra pars compacta (SNpc) and widespread aggregates of the protein α-synuclein (α-syn). Recently, microRNAs, small, noncoding RNAs involved in regulating gene expression at the posttranscriptional level, have been recognized as important regulators of the inflammatory environment. Using an array approach, we found significant upregulation of microRNA-155 (miR-155) in an in vivo model of PD produced by adeno-associated-virus-mediated expression of α-syn. Using a mouse with a complete deletion of miR-155, we found that loss of miR-155 reduced proinflammatory responses to α-syn and blocked α-syn-induced neurodegeneration. In primary microglia from miR-155(-/-) mice, we observed a markedly reduced inflammatory response to α-syn fibrils, with attenuation of major histocompatibility complex class II (MHCII) and proinflammatory inducible nitric oxide synthase expression. Treatment of these microglia with a synthetic mimic of miR-155 restored the inflammatory response to α-syn fibrils. Our results suggest that miR-155 has a central role in the inflammatory response to α-syn in the brain and in α-syn-related neurodegeneration. These effects are at least in part due to a direct role of miR-155 on the microglial response to α-syn. These data implicate miR-155 as a potential therapeutic target for regulating the inflammatory response in PD. PMID:26911687

  1. Neuroprotective Effects of Germinated Brown Rice in Rotenone-Induced Parkinson's-Like Disease Rats.

    PubMed

    Chompoopong, Supin; Jarungjitaree, Sunit; Punbanlaem, Tideeporn; Rungruang, Thanaporn; Chongthammakun, Sukumal; Kettawan, Aikkarach; Taechowisan, Thongchai

    2016-09-01

    The effects of germinated brown rice (GBR) on the motor deficits and the dopaminergic (DA) cell death were investigated in Parkinson's-like disease (PD) rats. Reactive oxidative species generated by chronic subcutaneous injection of rotenone (RT) lead to neuronal apoptosis particularly in the nigrostriatal DA system and produce many features of PD, bradykinesis, postural instability and rigidity. In this study, 4-phenylbutyric acid (4-PBA), previously reported to inhibit RT-induced DA cell death, was used as the positive control. Results show that pretreatment with GBR as well as 4-PBA significantly enhanced the motor activity after RT injection, and GBR affected significantly in open field test, only in the ambulation but not the mobility duration, and ameliorated the time to orient down (t-turn) and total time to descend the pole (t-total) in pole test as compared to RT group, but significantly lowered both t-turn and t-total only in 4-PBA group. The percentage of apoptotic cells in brain measured by flow cytometry and the inflammatory effect measured by ELISA of TNF-α showed significant increase in RT group as compared to the control (CT) group at P < 0.05. Apoptotic cells in RT group (85.98 %) showed a significant (P < 0.05) increase versus CT group (17.50 %), and this effect was attenuated in GBR+RT group by decreasing apoptotic cells (79.32 %), whereas, increased viable cells (17.94 %) versus RT group (10.79 %). GBR in GBR + RT group could decrease TNF-α both in the serum and in brain. In summary, GBR showed a neuroprotective effect in RT-induced PD rats, and it may be useful as a value-added functional food to prevent neurodegenerative disease or PD. PMID:27430236

  2. Neuroprotective effect of Tinospora cordifolia ethanol extract on 6-hydroxy dopamine induced Parkinsonism

    PubMed Central

    Kosaraju, Jayasankar; Chinni, Santhivardhan; Roy, Partha Deb; Kannan, Elango; Antony, A. Shanish; Kumar, M. N. Satish

    2014-01-01

    Objective: The present study investigates the neuroprotective activity of ethanol extract of Tinospora cordifolia aerial parts against 6-hydroxy dopamine (6-OHDA) lesion rat model of Parkinson's disease (PD). Materials and Methods: T. cordifolia ethanol extract (TCEE) was standardized with high performance thin layer chromatography using berberine. Experimental PD was induced by intracerebral injection of 6-OHDA (8 μg). Animals were divided into five groups: sham operated, negative control, positive control (levodopa 6 mg/kg) and two experimental groups (n = 6/group). Experimental groups received 200 and 400 mg/kg of TCEE once daily for 30 days by oral gavage. Biochemical parameters including dopamine level, oxidative stress, complex I activity and brain iron asymmetry ratio and locomotor activity including skeletal muscle co-ordination and degree of catatonia were assessed. Results: TCEE exhibited significant neuroprotection by increasing the dopamine levels (1.96 ± 0.20 and 2.45 ± 0.40 ng/mg of protein) and complex I activity (77.14 ± 0.89 and 78.50 ± 0.96 nmol/min/mg of protein) at 200 and 400 mg/kg respectively when compared with negative control group. Iron asymmetry ratio was also significantly attenuated by TCEE at 200 (1.57 ± 0.18) and 400 mg/kg (1.11 ± 0.15) when compared with negative control group. Neuroprotection by TCEE was further supported by reduced oxidative stress and restored locomotor activity in treatment groups. Conclusion: Results show that TCEE possess significant neuroprotection in 6-OHDA induced PD by protecting dopaminergic neurons and reducing the iron accumulation. PMID:24741189

  3. Parkinson's disease-linked mutations in VPS35 induce dopaminergic neurodegeneration.

    PubMed

    Tsika, Elpida; Glauser, Liliane; Moser, Roger; Fiser, Aris; Daniel, Guillaume; Sheerin, Una-Marie; Lees, Andrew; Troncoso, Juan C; Lewis, Patrick A; Bandopadhyay, Rina; Schneider, Bernard L; Moore, Darren J

    2014-09-01

    Mutations in the vacuolar protein sorting 35 homolog (VPS35) gene at the PARK17 locus, encoding a key component of the retromer complex, were recently identified as a new cause of late-onset, autosomal dominant Parkinson's disease (PD). Here we explore the pathogenic consequences of PD-associated mutations in VPS35 using a number of model systems. VPS35 exhibits a broad neuronal distribution throughout the rodent brain, including within the nigrostriatal dopaminergic pathway. In the human brain, VPS35 protein levels and distribution are similar in tissues from control and PD subjects, and VPS35 is not associated with Lewy body pathology. The common D620N missense mutation in VPS35 does not compromise its protein stability or localization to endosomal and lysosomal vesicles, or the vesicular sorting of the retromer cargo, sortilin, SorLA and cation-independent mannose 6-phosphate receptor, in rodent primary neurons or patient-derived human fibroblasts. In yeast we show that PD-linked VPS35 mutations are functional and can normally complement VPS35 null phenotypes suggesting that they do not result in a loss-of-function. In rat primary cortical cultures the overexpression of human VPS35 induces neuronal cell death and increases neuronal vulnerability to PD-relevant cellular stress. In a novel viral-mediated gene transfer rat model, the expression of D620N VPS35 induces the marked degeneration of substantia nigra dopaminergic neurons and axonal pathology, a cardinal pathological hallmark of PD. Collectively, these studies establish that dominant VPS35 mutations lead to neurodegeneration in PD consistent with a gain-of-function mechanism, and support a key role for VPS35 in the development of PD. PMID:24740878

  4. Drug induced acute pancreatitis: Does it exist?

    PubMed Central

    Tenner, Scott

    2014-01-01

    As the incidence of acute pancreatitis continues to rise, establishing the etiology in order to prevent recurrence is important. Although the etiology of acute pancreatitis is not difficult in the majority of patients, almost a quarter of patients are initially labeled as having idiopathic acute pancreatitis. When confronted with a patient with acute pancreatitis and no clear etiology defined as an absence alcoholism, gallstones (ultrasound and/or MRI), a normal triglyceride level, and absence of tumor, it often appears reasonable to consider a drug as the cause of acute pancreatitis. Over 100 drugs have been implicated by case reports as causing acute pancreatitis. While some of these case reports are well written, many case reports represent poorly written experiences of the clinician simply implicating a drug without a careful evaluation. Over-reliance on case reports while ignoring randomized clinical trials and large pharmacoepidemiologic surveys has led to confusion about drug induced acute pancreatitis. This review will explain that drug induced acute pancreatitis does occur, but it is rare, and over diagnosis leads to misconceptions about the disease resulting in inappropriate patient care, increased litigation and a failure to address the true entity: idiopathic acute pancreatitis. PMID:25469020

  5. Drug induced acute pancreatitis: does it exist?

    PubMed

    Tenner, Scott

    2014-11-28

    As the incidence of acute pancreatitis continues to rise, establishing the etiology in order to prevent recurrence is important. Although the etiology of acute pancreatitis is not difficult in the majority of patients, almost a quarter of patients are initially labeled as having idiopathic acute pancreatitis. When confronted with a patient with acute pancreatitis and no clear etiology defined as an absence alcoholism, gallstones (ultrasound and/or MRI), a normal triglyceride level, and absence of tumor, it often appears reasonable to consider a drug as the cause of acute pancreatitis. Over 100 drugs have been implicated by case reports as causing acute pancreatitis. While some of these case reports are well written, many case reports represent poorly written experiences of the clinician simply implicating a drug without a careful evaluation. Over-reliance on case reports while ignoring randomized clinical trials and large pharmacoepidemiologic surveys has led to confusion about drug induced acute pancreatitis. This review will explain that drug induced acute pancreatitis does occur, but it is rare, and over diagnosis leads to misconceptions about the disease resulting in inappropriate patient care, increased litigation and a failure to address the true entity: idiopathic acute pancreatitis. PMID:25469020

  6. Ameliorative effect of Sida cordifolia in rotenone induced oxidative stress model of Parkinson's disease.

    PubMed

    Khurana, Navneet; Gajbhiye, Asmita

    2013-12-01

    Present study focused on the evaluation of aqueous extract of Sida cordifolia (AESC), and its different fractions; hexane (HFSC), chloroform (CFSC) and aqueous (AFSC), against rotenone induced biochemical, neurochemical, histopathological and behavioral alterations in a rat model of Parkinson's disease (PD). An estimation of the level of thiobarbituric acid reactive substances (TBARS), glutathione (GSH) and catalase (CAT) along with superoxide anion generation (SAG) in different brain regions (cortex, midbrain and cerebellum) was carried out to assess biochemical changes. Behavioral evaluation tests (catalepsy, rearing behavior and posture instability) and neurochemical estimations (norepinephrine, dopamine and serotonin level) along with histopathological evaluations of different brain regions were also performed. The varying doses (50, 100, 250mg/kg; p.o.) of different test treatments (AESC, HFSC, CFSC and AFSC) were co-administered along with rotenone (2mg/kg; s.c.), for a period of 35 days to rats of various groups and compared with rotenone per se (negative control) and l-deprenyl (positive control; 10mg/kg; p.o.) treated groups for the above mentioned parameters. The increase in catalepsy and posture instability along with decrease in rearing behavior observed due to rotenone treatment was significantly attenuated by co-treatment with varying doses of AESC and AFSC. Results of the histopathological studies of different brain regions of rats showed eosinophilic lesions in the mid brain region due to rotenone treatment. The eosinophilic lesions were significantly attenuated in co-treated groups of AESC-100mg/kg and AFSC-100mg/kg. Rotenone induced oxidative damage, revealed by increased level of TBARS, SAG and decreased level of GSH and CAT in mid brain region of rats, was attenuated by the co-treatment of AESC and AFSC. The rotenone induced decrease of dopamine level in the midbrain region of rats was also attenuated by co-treatment of AESC-100mg/kg and AFSC

  7. Drug-Induced Hyperglycaemia and Diabetes.

    PubMed

    Fathallah, Neila; Slim, Raoudha; Larif, Sofien; Hmouda, Houssem; Ben Salem, Chaker

    2015-12-01

    Drug-induced hyperglycaemia and diabetes is a global issue. It may be a serious problem, as it increases the risk of microvascular and macrovascular complications, infections, metabolic coma and even death. Drugs may induce hyperglycaemia through a variety of mechanisms, including alterations in insulin secretion and sensitivity, direct cytotoxic effects on pancreatic cells and increases in glucose production. Antihypertensive drugs are not equally implicated in increasing serum glucose levels. Glycaemic adverse events occur more frequently with thiazide diuretics and with certain beta-blocking agents than with calcium-channel blockers and inhibitors of the renin-angiotensin system. Lipid-modifying agents may also induce hyperglycaemia, and the diabetogenic effect seems to differ between the different types and daily doses of statins. Nicotinic acid may also alter glycaemic control. Among the anti-infectives, severe life-threatening events have been reported with fluoroquinolones, especially when high doses are used. Protease inhibitors and, to a lesser extent, nucleoside reverse transcriptase inhibitors have been reported to induce alterations in glucose metabolism. Pentamidine-induced hyperglycaemia seems to be related to direct dysfunction in pancreatic cells. Phenytoin and valproic acid may also induce hyperglycaemia. The mechanisms of second-generation antipsychotic-associated hyperglycaemia, diabetes mellitus and ketoacidosis are complex and are mainly due to insulin resistance. Antidepressant agents with high daily doses seem to be more frequently associated with an increased risk of diabetes. Ketoacidosis may occur in patients receiving beta-adrenergic stimulants, and theophylline may also induce hyperglycaemia. Steroid diabetes is more frequently associated with high doses of glucocorticoids. Some chemotherapeutic agents carry a higher risk of hyperglycaemia, and calcineurin inhibitor-induced hyperglycaemia is mainly due to a decrease in insulin secretion

  8. Neuroprotective Effect of Coptis chinensis in MPP[Formula: see text] and MPTP-Induced Parkinson's Disease Models.

    PubMed

    Friedemann, Thomas; Ying, Yue; Wang, Weigang; Kramer, Edgar R; Schumacher, Udo; Fei, Jian; Schröder, Sven

    2016-01-01

    The rhizome of Coptis chinensis is commonly used in traditional Chinese medicine alone or in combination with other herbs to treat diseases characterized by causing oxidative stress including inflammatory diseases, diabetes mellitus and neurodegenerative diseases. In particular, there is emerging evidence that Coptis chinensis is effective in the treatment of neurodegenerative diseases associated with oxidative stress. Hence, the aim of this study was to investigate the neuroprotective effect of Coptis chinensis in vitro and in vivo using MPP[Formula: see text] and MPTP models of Parkinson's disease. MPP[Formula: see text] treated human SH-SY5Y neuroblastoma cells were used as a cell model of Parkinson's disease. A 24[Formula: see text]h pre-treatment of the cells with the watery extract of Coptis chinensis significantly increased cell viability, as well as the intracellular ATP concentration and attenuated apoptosis compared to the MPP[Formula: see text] control. Further experiments with the main alkaloids of Coptidis chinensis, berberine, coptisine, jaterorrhizine and palmatine revealed that berberine and coptisine were the main active compounds responsible for the observed neuroprotective effect. However, the full extract of Coptis chinensis was more effective than the tested single alkaloids. In the MPTP-induced animal model of Parkinson's disease, Coptis chinensis dose-dependently improved motor functions and increased tyrosine hydroxylase-positive neurons in the substantia nigra compared to the MPTP control. Based on the results of this work, Coptis chinensis and its main alkaloids could be considered potential candidates for the development of new treatment options for Parkinson's disease. PMID:27430912

  9. Overground robot assisted gait trainer for the treatment of drug-resistant freezing of gait in Parkinson disease.

    PubMed

    Pilleri, Manuela; Weis, Luca; Zabeo, Letizia; Koutsikos, Konstantinos; Biundo, Roberta; Facchini, Silvia; Rossi, Simonetta; Masiero, Stefano; Antonini, Angelo

    2015-08-15

    Freezing of Gait (FOG) is a frequent and disabling feature of Parkinson disease (PD). Gait rehabilitation assisted by electromechanical devices, such as training on treadmill associated with sensory cues or assisted by gait orthosis have been shown to improve FOG. Overground robot assisted gait training (RGT) has been recently tested in patients with PD with improvement of several gait parameters. We here evaluated the effectiveness of RGT on FOG severity and gait abnormalities in PD patients. Eighteen patients with FOG resistant to dopaminergic medications were treated with 15 sessions of RGT and underwent an extensive clinical evaluation before and after treatment. The main outcome measures were FOG questionnaire (FOGQ) global score and specific tasks for gait assessment, namely 10 meter walking test (10 MWT), Timed Up and Go test (TUG) and 360° narrow turns (360 NT). Balance was also evaluated through Fear of Falling Efficacy Scale (FFES), assessing self perceived stability and Berg Balance Scale (BBS), for objective examination. After treatment, FOGQ score was significantly reduced (P=0.023). We also found a significant reduction of time needed to complete TUG, 10 MWT, and 360 NT (P=0.009, 0.004 and 0.04, respectively). By contrast the number of steps and the number of freezing episodes recorded at each gait task did not change. FFES and BBS scores also improved, with positive repercussions on performance on daily activity and quality of life. Our results indicate that RGT is a useful strategy for the treatment of drug refractory FOG. PMID:26048047

  10. An update on pharmacological, pharmacokinetic properties and drug-drug interactions of rotigotine transdermal system in Parkinson's disease and restless legs syndrome.

    PubMed

    Elshoff, Jan-Peer; Cawello, Willi; Andreas, Jens-Otto; Mathy, Francois-Xavier; Braun, Marina

    2015-04-01

    This narrative review reports on the pharmacological and pharmacokinetic properties of rotigotine, a non-ergolinic D₃/D₂/D₁ dopamine receptor agonist approved for the treatment of early- and advanced-stage Parkinson's disease (PD) and moderate to severe restless legs syndrome (RLS). Rotigotine is formulated as a transdermal patch providing continuous drug delivery over 24 h, with a plasma concentration profile similar to that of administration via continuous intravenous infusion. Absolute bioavailability after 24 h transdermal delivery is 37 % of the applied rotigotine dose. Following a single administration of rotigotine transdermal system (24-h patch-on period), most of the absorbed drug is eliminated in urine and feces as sulphated and glucuronidated conjugates within 24 h of patch removal. The drug shows a high apparent volume of distribution (>2500 L) and a total body clearance of 300-600 L/h. Rotigotine transdermal system provides dose-proportional pharmacokinetics up to supratherapeutic dose rates of 24 mg/24 h, with steady-state plasma drug concentrations attained within 1-2 days of daily dosing. The pharmacokinetics of rotigotine transdermal patch are similar in healthy subjects, patients with early- or advanced-stage PD, and patients with RLS when comparing dose-normalized area under the plasma concentration-time curve (AUC) and maximum plasma drug concentration (Cmax), as well as half-life and other pharmacokinetic parameters. Also, it is not influenced in a relevant manner by age, sex, ethnicity, advanced renal insufficiency, or moderate hepatic impairment. No clinically relevant drug-drug interactions were observed following co-administration of rotigotine with levodopa/carbidopa, domperidone, or the CYP450 inhibitors cimetidine or omeprazole. Also, pharmacodynamics and pharmacokinetics of an oral hormonal contraceptive were not influenced by rotigotine co-administration. Rotigotine was generally well tolerated, with an adverse event profile

  11. Is there room for non-dopaminergic treatment in Parkinson disease?

    PubMed

    Lieberman, Abraham; Krishnamurthi, Narayanan

    2013-02-01

    Although levodopa and dopaminergic drugs remain the mainstay of therapy for the motor symptoms of Parkinson disease (PD), they fail to address many of the non-motor symptoms of PD including orthostatic hypotension, freezing of gait (FOG) and difficulty with balance, drug-induced paranoia and hallucinations, and drug-induced dyskinesias. Droxidopa, a drug that increases norepinephrine, treats orthostatic hypotension, cholinomimetic drugs sometimes help with FOG and difficulty with balance, pimavanserin, a drug that blocks serotonin receptors, treats paranoia and hallucinations, and anti-glutaminergic drugs treat dyskinesias. Thus, there are ample opportunities for non-dopaminergic drugs in PD. PMID:23242741

  12. Parkinson's disease-like forelimb akinesia induced by BmK I, a sodium channel modulator.

    PubMed

    Zhu, Hongyan; Wang, Ziyi; Jin, Jiahui; Pei, Xiao; Zhao, Yuxiao; Wu, Hao; Lin, Weide; Tao, Jie; Ji, Yonghua

    2016-07-15

    Parkinson's disease (PD) is a neurodegenerative disorder and characterized by motor disabilities which are mostly linked with high levels of synchronous oscillations in the basal ganglia neurons. Voltage-gated sodium channels (VGSCs) play a vital role in the abnormal electrical activity of neurons in the globus pallidus (GP) and the subthalamic nucleus (STN) in PD. BmK I, a α-like toxin purified from the Chinese scorpion Buthus martensi Karsch, has been identified a site-3-specific modulator of VGSCs. The present study shows that forelimb akinesia can be induced by the injection of BmK I into the globus pallidus (GP) in rats. In addition, BmK I cannot produce neuronal damage in vivo and in vitro at 24h after treatment, indicating that the forelimb akinesia does not result from neuronal damage. Electrophysiological studies further revealed that the inactivated Na(+) currents were showed to be more vulnerably modulated by BmK I than the activated Na(+) currents in human neuron-like SHSY5Y cells. Furthermore, the modulation of BmK I on inactivation was preferentially attributed to fast inactivation rather than slow inactivation. Therefore, the PD-like forelimb akinesia may result from the modulation of sodium channels in neuron by BmK I. These findings not only suggest that BmK I may be an effective and novel molecule for the study of pathogenesis in PD but also support the idea that VGSCs play a crucial role in the motor disabilities in PD. PMID:27108049

  13. Blood dyscrasias induced by psychotropic drugs.

    PubMed

    Stübner, S; Grohmann, R; Engel, R; Bandelow, B; Ludwig, W-D; Wagner, G; Müller-Oerlinghausen, B; Möller, H-J; Hippius, H; Rüther, E

    2004-03-01

    Drugs can cause a variety of blood dyscrasias, e. g., by interfering with hematopoiesis in the bone marrow or damaging mature blood cells by antibodies. Although numerous reports on the risks of adverse hematological effects associated with psychotropic drugs have led to stringent monitoring requirements for some compounds, particularly neuroleptics, it is still difficult to estimate the true prevalence of such risks. Sixteen episodes of thrombocytopenia, 63 of neutropenia, 22 of agranulocytosis, 4 episodes of severe neutro- and thrombocytopenia, and 2 of pancytopenia were documented by the drug safety program in psychiatry AMSP (Arzneimittelsicherheit in der Psychiatrie) in a population of 122,562 patients between 1993 and 2000. All cases were related to the epidemiological data provided for this population and systematically analyzed as regards history of medication, co-medication, and the clinical course. Putative risk rates for the main groups of medications and a number of drugs could be estimated with this database. Most changes in the white blood cell counts, which were rated as probably or definitely drug-induced, were attributed to clozapine (0.18 % of patients exposed), carbamazepine (0.14 %) and perazine (0.09 %). In patients on newer atypical neuroleptics, we documented neutropenia assumed to be probably or definitely drug-related in five patients during treatment with olanzapine and in one case with risperidone. In all five olanzapine-related cases, the drugs were the sole cause of the adverse drug reactions. All surveyed patients who received clozapine showed no difference in age and gender distribution from those who developed hematological changes. Incidences of hematological changes for antidepressants were much lower (about 0.01 %). Although the methodological accuracy of these findings has to be critically discussed these data could be of considerable clinical relevance and should be helpful in making clinical treatment decisions. PMID:15052517

  14. Parkinson's Disease

    MedlinePlus

    ... results in reduction of a critical neurotransmitter called dopamine, a chemical responsible for transmitting messages to parts ... that coordinate muscle movement. Parkinson's patients have less dopamine. Studies have shown that the symptoms of Parkinson's ...

  15. Parkinson's Disease

    MedlinePlus

    ... about 5 to 10 percent of people with Parkinson's have "early-onset" disease which begins before the age of 50. Early-onset forms of Parkinson's are often inherited, though not always, and some ...

  16. Meprobamate-induced fixed drug eruption.

    PubMed

    Zaïem, Ahmed; Kaabi, Widd; Badri, Talel; Lakhoua, Ghozlane; Sahnoun, Rym; Kastalli, Sarrah; Daghfous, Riadh; Lakhal, Mohamed; El Aidli, Sihem

    2014-01-01

    Meprobamate is usually a safe drug prescribed for anxiety disorders. Fixed drug eruption (FDE) is an exceptional cutaneous adverse effect of this drug. We report a case of FDE induced by meprobamate with positive patch test. A 22-year-old woman was prescribed for depression meprobamate, aceprometazine, valpromide and lorazepam. On the second day of treatment, the patient presented red erythematous and pruriginous plaques in the limbs and the face. After stopping the previous treatment, the patient's lesions resolved completely within 3 weeks with residual pigmentation. One month later, patch tests were performed and were positive to meprobamate. Exceptional cases of FDE were reported in literature with meprobamate. None has reported the use of patch test to confirm the diagnosis. PMID:24446836

  17. Zhichan decoction induces differentiation of dopaminergic neurons in Parkinson's disease rats after neural stem cell transplantation

    PubMed Central

    Shi, Huifen; Song, Jie; Yang, Xuming

    2014-01-01

    The goal of this study was to increase the dopamine content and reduce dopaminergic metabolites in the brain of Parkinson's disease rats. Using high-performance liquid chromatography, we found that dopamine and dopaminergic metabolite (dihydroxyphenylacetic acid and homovanillic acid) content in the midbrain of Parkinson's disease rats was increased after neural stem cell transplantation + Zhichan decoction, compared with neural stem cell transplantation alone. Our genetic algorithm results show that dihydroxyphenylacetic acid and homovanillic acid levels achieve global optimization. Neural stem cell transplantation + Zhichan decoction increased dihydroxyphenylacetic acid levels up to 10-fold, while transplantation alone resulted in a 3-fold increment. Homovanillic acid levels showed no apparent change. Our experimental findings show that after neural stem cell transplantation in Parkinson's disease rats, Zhichan decoction can promote differentiation of neural stem cells into dopaminergic neurons. PMID:25206914

  18. [Depression in Parkinson's disease].

    PubMed

    Murata, Miho; Okamoto, Tomoko

    2013-01-01

    The frequency of depression in patients with Parkinson's disease is approximately 30-40%. Depression has a significantly negative impact on the QOL in Parkinson's disease patients. It leads to the worsening of tremors and frozen gait without disease progression and decreases the patient's motivation to participate in rehabilitation. The distinguishing feature of depression in patients with Parkinson's disease is that guilt, self-blame and suicidal ideation are rarely seen compared to that observed in patients with major depression. Depression can occur in the pre-motor, diagnostic and advanced stages of Parkinson's disease. In particular, patients with wearing-off symptoms are apt to develop anxiety. As for treatment, it is very important to optimize dopamine replacement therapy. Antiparkinsonian drugs may have beneficial effects not only on the motor symptoms of the disease, but also the patient's mood. Cognitive behavioral therapy (CBT) and peer counseling may also be beneficial. PMID:24622217

  19. Drug-induced mitochondrial dysfunction and cardiotoxicity.

    PubMed

    Varga, Zoltán V; Ferdinandy, Peter; Liaudet, Lucas; Pacher, Pál

    2015-11-01

    Mitochondria has an essential role in myocardial tissue homeostasis; thus deterioration in mitochondrial function eventually leads to cardiomyocyte and endothelial cell death and consequent cardiovascular dysfunction. Several chemical compounds and drugs have been known to directly or indirectly modulate cardiac mitochondrial function, which can account both for the toxicological and pharmacological properties of these substances. In many cases, toxicity problems appear only in the presence of additional cardiovascular disease conditions or develop months/years following the exposure, making the diagnosis difficult. Cardiotoxic agents affecting mitochondria include several widely used anticancer drugs [anthracyclines (Doxorubicin/Adriamycin), cisplatin, trastuzumab (Herceptin), arsenic trioxide (Trisenox), mitoxantrone (Novantrone), imatinib (Gleevec), bevacizumab (Avastin), sunitinib (Sutent), and sorafenib (Nevaxar)], antiviral compound azidothymidine (AZT, Zidovudine) and several oral antidiabetics [e.g., rosiglitazone (Avandia)]. Illicit drugs such as alcohol, cocaine, methamphetamine, ecstasy, and synthetic cannabinoids (spice, K2) may also induce mitochondria-related cardiotoxicity. Mitochondrial toxicity develops due to various mechanisms involving interference with the mitochondrial respiratory chain (e.g., uncoupling) or inhibition of the important mitochondrial enzymes (oxidative phosphorylation, Szent-Györgyi-Krebs cycle, mitochondrial DNA replication, ADP/ATP translocator). The final phase of mitochondrial dysfunction induces loss of mitochondrial membrane potential and an increase in mitochondrial oxidative/nitrative stress, eventually culminating into cell death. This review aims to discuss the mechanisms of mitochondrion-mediated cardiotoxicity of commonly used drugs and some potential cardioprotective strategies to prevent these toxicities. PMID:26386112

  20. [Drug-induced impairment of renal function].

    PubMed

    Krüger, B; Benck, U; Singer, T; Krämer, B K

    2012-09-01

    Acute kidney injury (AKI) of any origin is a common complication/disease in hospitalized patients, going along with significantly increased mortality and morbidity, as well as hospitalization duration and expenses. Drug-induced AKI is usually seen in patients with concurrent risk factors such as existing kidney disease, dehydration with or without hypotension, older age or diabetes mellitus. In cases with multiple risk factors or therapies the triggering drug is often impossible to define. Hemodynamic alterations, intrinsic tubulointerstitial damages and intrarenal (i. e. tubular) obstructions as a result of drug precipitations are the pathophysiological basis of this disease entity. Clinically the AKI is perceived as the most important problem, due to the development of hyperhydration (including pulmonary edema) and reduced/lacking clearance of toxic metabolites. The prognosis of drug-induced AKI is usually good, especially if the agents are stopped early in the process, but nevertheless some patients experience severe acute AKI requiring dialysis with/without subsequent restoration. Considering and recognizing potential risk factors may help to identify patients at risk and lead to introduction of prophylactic actions. Identification of risk factors and the introduction of prevention strategies should be an integral part of everybody's daily clinical work, especially in intensive care medicine due to the high susceptibility to AKI. PMID:22971974

  1. Acute and chronic drug-induced hepatitis.

    PubMed

    Pessayre, D; Larrey, D

    1988-04-01

    Adverse drug reactions may mimic almost any kind of liver disease. Acute hepatitis is often due to the formation of reactive metabolites in the liver. Despite several protective mechanisms (epoxide hydrolases, conjugation with glutathione), this formation may lead to predictable toxic hepatitis after hugh overdoses (e.g. paracetamol), or to idiosyncratic toxic hepatitis after therapeutic doses (e.g. isoniazid). Both genetic factors (e.g. constitutive levels of cytochrome P-450 isoenzymes, or defects in protective mechanisms) and acquired factors (e.g. malnutrition, or chronic intake of alcohol or other microsomal enzyme inducers) may explain the unique susceptibility of some patients. Formation of chemically reactive metabolites may also lead to allergic hepatitis, probably through immunization against plasma membrane protein epitopes modified by the covalent binding of the reactive metabolites. This may be the mechanism for acute hepatitis produced by many drugs (e.g. amineptine, erythromycin derivatives, halothane, imipramine, isaxonine, alpha-methyldopa, tienilic acid, etc.). Genetic defects in several protective mechanisms (e.g. epoxide hydrolase, acetylation) may explain the unique susceptibility of some patients, possibly by increasing exposure to allergenic, metabolite-altered plasma membrane protein epitopes. Like toxic idiosyncratic hepatitis, allergic hepatitis occurs in a few patients only. Unlike toxic hepatitis, allergic hepatitis is frequently associated with fever, rash or other hypersensitivity manifestations; it may be hepatocellular, mixed or cholestatic; it promptly recurs after inadvertent drug rechallenge. Lysosomal phospholipidosis occurs frequently with three antianginal drugs (diethylaminoethoxyhexestrol, amiodarone and perhexiline). These cationic, amphiphilic drugs may form phospholipid-drug complexes within lysosomes. Such complexes resist phospholipases and accumulate within enlarged lysosomes, forming myeloid figures. This

  2. Inhibition of Endoplasmic Reticulum Stress is Involved in the Neuroprotective Effect of bFGF in the 6-OHDA-Induced Parkinson's Disease Model.

    PubMed

    Cai, Pingtao; Ye, Jingjing; Zhu, Jingjing; Liu, Dan; Chen, Daqing; Wei, Xiaojie; Johnson, Noah R; Wang, Zhouguang; Zhang, Hongyu; Cao, Guodong; Xiao, Jian; Ye, Junming; Lin, Li

    2016-08-01

    Parkinson's disease (PD) is a progressive neurodegenerative disorder with complicated pathophysiologic mechanisms. Endoplasmic reticulum (ER) stress appears to play a critical role in the progression of PD. We demonstrated that basic fibroblast growth factor (bFGF), as a neurotropic factor, inhibited ER stress-induced neuronal cell apoptosis and that 6-hydroxydopamine (6-OHDA)-induced ER stress was involved in the progression of PD in rats. bFGF administration improved motor function recovery, increased tyrosine hydroxylase (TH)-positive neuron survival, and upregulated the levels of neurotransmitters in PD rats. The 6-OHDA-induced ER stress response proteins were inhibited by bFGF treatment. Meanwhile, bFGF also increased expression of TH. The administration of bFGF activated the downstream signals PI3K/Akt and Erk1/2 in vivo and in vitro. Inhibition of the PI3K/Akt and Erk1/2 pathways by specific inhibitors partially reduced the protective effect of bFGF. This study provides new insight towards bFGF translational drug development for PD involving the regulation of ER stress. PMID:27493838

  3. Subthalamic 6-OHDA-induced lesion attenuates levodopa-induced dyskinesias in the rat model of Parkinson's disease.

    PubMed

    Marin, C; Bonastre, M; Mengod, G; Cortés, R; Rodríguez-Oroz, M C; Obeso, J A

    2013-12-01

    The subthalamic nucleus (STN) receives direct dopaminergic innervation from the substantia nigra pars compacta that degenerates in Parkinson's disease. The present study aimed to investigate the role of dopaminergic denervation of STN in the origin of levodopa-induced dyskinesias. Rats were distributed in four groups which were concomitantly lesioned with 6-OHDA or vehicle (sham) in the STN and in the medial forebrain bundle (MFB) as follows: a) MFB-sham plus STN-sham, b) MFB-sham plus STN-lesion, c) MFB-lesion plus STN-sham, and d) MFB-lesion plus STN-lesion. Four weeks after lesions, animals were treated with levodopa (6mg/kg with 15mg/kg benserazide i.p.) twice daily for 22 consecutive days. Abnormal involuntary movements were measured. In situ hybridization was performed measuring the expression of striatal preproenkephalin, preprodynorphin, STN cytochrome oxidase (CO) and nigral GAD67 mRNAs. STN 6-OHDA denervation did not induce dyskinesias in levodopa-treated MFB-sham animals but attenuated axial (p<0.05), limb (p<0.05) and orolingual (p<0.01) dyskinesias in rats with a concomitant lesion of the nigrostriatal pathway. The attenuation of dyskinesias was associated with a decrease in the ipsilateral STN CO mRNA levels (p<0.05). No significant differences between MFB-lesion plus STN-sham and MFB-lesion plus STN-lesion groups in the extent of STN dopaminergic denervation were observed. Moreover, intrasubthalamic microinfusion of dopamine in the MFB-lesion plus STN-lesion group triggered orolingual (p<0.01), but not axial or limb, dyskinesias. These results suggest that dopaminergic STN innervation influences the expression of levodopa-induced dyskinesias but also the existence of non dopaminergic-mediated mechanisms. STN noradrenergic depletion induced by 6-OHDA in the STN needs to be taken in account as a possible mechanism explaining the attenuation of dyskinesias in the combined lesion group. PMID:24140562

  4. Evaluation of the Short Parkinson's Evaluation Scale: a new friendly scale for the evaluation of Parkinson's disease in clinical drug trials.

    PubMed

    Rabey, J M; Bass, H; Bonuccelli, U; Brooks, D; Klotz, P; Korczyn, A D; Kraus, P; Martinez-Martin, P; Morrish, P; Van Sauten, W; Van Hilten, B

    1997-08-01

    The extensive use of the Unified Parkinson's Disease Rating Scale (UPDRS) has revealed low interrater reliability in some items and redundancy in others. In view of these shortcomings, we have structured a new scale that includes a zero-to three-point scale for each item in the evaluation of PD. The mental axis includes memory, thought disorders, and depression. Activities of daily living (ADL) includes eight items: speech, eating, feeding, dressing, hygiene, handwriting, walking, and turning in bed. The motor examination includes eight items: speech, tremor, rest and posture, rigidity, finger tapping, arising from chair, gait, and postural stability. Complications of therapy were also included: dyskinesias, dystonia, motor fluctuations, and freezing episodes, collected by history. In addition, a global scoring for motor fluctuations that should complement the Hoehn and Yahr Scale was incorporated. In this report, we present a statistical analysis of the ADL, motor evaluation, and complications of therapy sections. Concerning the interrater reliability mean, Kendall's W values were >0.9 for most of the items in the Short Parkinson's Evaluation Scale (SPES). Kendall's W <0.8 (motor evaluation) was found for two items of the SPES and nine items of the UPDRS. The mean interrater reliability for both scales across all seven centers (seven Kendall's W for seven centers) (Mann-Whitney test) showed no statistical differences between the scales. Spearman's correlations between items of both scales were significant. Factor analysis of the SPES and UPDRS data revealed a four-factor solution that explained approximately 60% of the data. All participating centers found the SPES easier to apply and quicker to complete, when compared with the UPDRS. The results obtained strongly favor the introduction of SPES for clinical practice. PMID:9260730

  5. e-Cadherin in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Induced Parkinson Disease

    PubMed Central

    Cataldi, Samuela; Codini, Michela; Hunot, Stéphane; Légeron, François-Pierre; Ferri, Ivana; Siccu, Paola; Sidoni, Angelo; Ambesi-Impiombato, Francesco Saverio; Beccari, Tommaso; Curcio, Francesco; Albi, Elisabetta

    2016-01-01

    Today a large number of studies are focused on clarifying the complexity and diversity of the pathogenetic mechanisms inducing Parkinson disease. We used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin that induces Parkinson disease, to evaluate the change of midbrain structure and the behavior of the anti-inflammatory factor e-cadherin, interleukin-6, tyrosine hydroxylase, phosphatase and tensin homolog, and caveolin-1. The results showed a strong expression of e-cadherin, variation of length and thickness of the heavy neurofilaments, increase of interleukin-6, and reduction of tyrosine hydroxylase known to be expression of dopamine cell loss, reduction of phosphatase and tensin homolog described to impair responses to dopamine, and reduction of caveolin-1 known to be expression of epithelial-mesenchymal transition and fibrosis. The possibility that the overexpression of the e-cadherin might be implicated in the anti-inflammatory reaction to MPTP treatment by influencing the behavior of the other analyzed molecules is discussed. PMID:27194825

  6. Acupuncture inhibits ferric iron deposition and ferritin-heavy chain reduction in an MPTP-induced parkinsonism model.

    PubMed

    Choi, Yeong-Gon; Park, Jae-Hyun; Lim, Sabina

    2009-01-30

    This study investigated the effect of acupuncture on iron-related oxidative damage in a mouse model designed as a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism model. To generate the chronic parkinsonism model, mice were intraperitoneally injected with MPTP (20mg/kg, one daily injection) for 30 days and acupuncture was performed at acupoints LR3 (Taichong) and GB34 (Yanglingquan) at 48h intervals. Acupuncture inhibited decreases in the immunoreactivities of tyrosine hydroxylase (TH) and dopamine transporter (DAT) that occurred as a result of MPTP neurotoxicity. The presence of ferric iron (Fe(3+)), but not ferrous iron (Fe(2+)), was strongly increased in the substantia nigra (SN) as a result of chronic loading of MPTP, whereas the ferritin-heavy chain (F-H) was significantly decreased. However, acupuncture treatment inhibited the increase in ferric iron and the decrease in the F-H that was induced by MPTP. Additionally, treatment with MPTP and acupuncture caused no changes in the presence of ferrous iron and ferritin-light chain (F-L) as a result of the treatments. The mRNA of F-H was also not affected. These results suggest that acupuncture may inhibit iron-related oxidative damage and may prevent the deleterious alteration of iron metabolism in the MPTP model. PMID:19056464

  7. Drug-Induced Rosacea-like Dermatitis.

    PubMed

    Rezaković, Saida; Bukvić Mokos, Zrinka; Paštar, Zrinjka

    2016-04-01

    Rosacea is a common, chronic cutaneous disorder with a prevalence of 0.5-10%, predominantly affecting women. The disease presents with a heterogeneous clinical picture characterized by transient flushing, persistent facial redness, telangiectasias, and, in more severe clinical forms, the presence of inflammatory papules and pustules in the central third of the face. Although its pathophysiology is complex and still remains unknown, factors that exacerbate the disease are well defined. They include genetic predisposition as well as external factors such as exposure to UV light, high temperature, and diet. Besides these well-known factors, recent studies suggest that drugs and vitamins could also be possible factors inducing rosacea-like dermatitis or aggravating pre-existing rosacea. Although these are less common possible triggering factors, the aim of this article is to present the current knowledge on the association between use of certain drugs or vitamins and rosacea. PMID:27149131

  8. Drug-induced lymphocyte stimulation test is not useful for the diagnosis of drug-induced pneumonia.

    PubMed

    Matsuno, Osamu; Okubo, Toshiyuki; Hiroshige, Shigeo; Takenaka, Rhyuichi; Ono, Emiko; Ueno, Takuya; Nureki, Shinichi; Ando, Masaru; Miyazaki, Eishi; Kumamoto, Toshihide

    2007-05-01

    Diagnosis of drug-induced pneumonia, which represents pulmonary toxicity caused by certain drugs, is difficult, as a large number of different drugs can elicit various immune-mediated diseases with distinct pathomechanisms. The drug-induced lymphocyte stimulation test (DLST) is widely used for diagnosing drug-induced pneumonia in Japan. Recent reports, however, indicate that DLST is not reliable for diagnosis of drug-induced pneumonia. To diagnose drug-induced pneumonia, a provocation test with the suspected drug is the most reliable method of assessing the relationship between the drug and pneumonia. We examined the correlation between the DLST and the provocation test in 6 cases of suspected drug-induced pneumonia. DLST was performed in all of the patients. The causes of pneumonia in all patients were confirmed by a provocation test. The DLST was positive in 3 of 6 cases of suspected drug-induced pneumonia, but the suspected drugs were ruled out by the provocation test. If we had relied solely on the DLST, these 3 cases would have been labeled as false allergy. The results of the DLST did not coincide with the results of the provocation test in any of the cases. Our results suggest that the DLST is not useful for the diagnosis of drug-induced pneumonia. Following provocation with the causative drug, reappearance of pulmonary infiltration was not observed in any of the cases. These findings indicate that a carefully performed provocation test is the safe and most reliable method. PMID:17464103

  9. Oleoylethanolamide reduces L-DOPA-induced dyskinesia via TRPV1 receptor in a mouse model of Parkinson´s disease.

    PubMed

    González-Aparicio, Ramiro; Moratalla, Rosario

    2014-02-01

    The long-term use of levodopa (L-DOPA) in Parkinson's disease (PD) results in the development of abnormal involuntary movements called L-DOPA-induced dyskinesias. Increasing evidences suggest that the endocannabinoid system may play a role in the modulation of dyskinesias. In this work, we assessed the antidyskinetic effect of the endocannabinoid analog oleoylethanolamide (OEA), an agonist of PPARα and antagonist of TRPV1 receptors. We used a hemiparkinsonian model of PD in mice with 6-OHDA striatal lesion. The chronic L-DOPA treatment developed intense axial, forelimb and orolingual dyskinetic symptoms, as well as contralateral rotations. Treatment with OEA reduced all these symptoms without reducing motor activity or the therapeutic motor effects of L-DOPA. Moreover, the OEA-induced reduction in dyskinetic behavior correlated with a reduction in molecular correlates of dyskinesia. OEA reduced FosB striatal overexpression and phosphoacetylation of histone 3, both molecular markers of L-DOPA-induced dyskinesias. We found that OEA antidyskinetic properties were mediated by TRPV1 receptor, as pretreatment with capsaicin, a TRPV1 agonist, blocked OEA antidyskinetic actions, as well as the reduction in FosB- and pAcH3-overexpression induced by L-DOPA. This study supports the hypothesis that the endocannabinoid system plays an important role in the development and expression of dyskinesias and might be an effective target for the treatment of L-DOPA-induced dyskinesias. Importantly, there was no development of tolerance to OEA in any of the parameters we examined, which has important implications for the therapeutic potential of drugs targeting the endocannabinoid system. PMID:24140894

  10. [Risk factors and subjective symptoms of drug-induced leucopenia].

    PubMed

    Hayashi, Kyoko; Ohtsu, Fumiko; Yano, Reiko; Sakakibara, Jinsaku; Goto, Nobuyuki

    2011-01-01

    The present study investigated risk factors and subjective symptoms associated with drug-induced leucopenia. We selected 248 patients with drug-induced leucopenia from the Case Reports of Adverse Drug Reactions and Poisoning Information System (CARPIS) database of over 47000 case reports of adverse drug reactions and assigned them to a case group. We also randomly selected 743 cases of adverse drug reactions not associated with leucopenia as a control group. A comparison of patient characteristic data between the two groups using logistic-regression analysis revealed that female sex, autoimmune disease and renal damage were background risk factors for drug-induced leucopenia. In addition, thiamazole, ritodrine, propylthiouracil, ticlopidine, allopurinol, minocycline and captopril administration significantly increased the risk of drug-induced leucopenia. A significant association was also found for fever, chills and pharyngeal abnormalities. Based on these findings, we developed two estimated regression equations to help prevent drug-induced leucopenia in the community pharmacy setting. PMID:21212623

  11. Role of serotonin neurons in the induction of levodopa- and graft-induced dyskinesias in Parkinson's disease.

    PubMed

    Carta, Manolo; Carlsson, Thomas; Muñoz, Ana; Kirik, Deniz; Björklund, Anders

    2010-01-01

    Recent studies in animal models of Parkinson's disease (PD) have provided evidence that dopamine released from spared serotonin afferents can act as a trigger of dyskinetic movements induced by repetitive, low doses of levodopa. Serotonin neurons have the capacity to store and release dopamine synthesized from systemically administered levodopa. However, because of the lack of any autoregulatory feedback control, dopamine released from serotonin terminals results in excessive swings in extracellular dopamine levels after peripheral administration of levodopa. Such "dysregulated" release of levodopa-derived dopamine is likely to be responsible for the appearance of the abnormal movements in levodopa-primed animals. This mechanism may also play a role in the development of graft-induced dyskinesias in patients that receive fetal neuron transplants, possibly due to the inclusion of serotonin neurons in the grafted ventral midbrain tissue, which contribute to maintain dopamine receptors of the denervated striatum in a supersensitive state. PMID:20187238

  12. Drug-induced erythrocyte membrane internalization

    PubMed Central

    Ben-Bassat, Isaac; Bensch, Klaus G.; Schrier, Stanley L.

    1972-01-01

    In vitro erythrocyte membrane internalization, resulting in the formation of membrane-lined vacuoles, can be quantified by a radioisotopic method. A complex of 37Co-labeled vitamin B12 and its plasma protein binders is first adsorbed to the cell surface, and after vacuoles are formed, the noninternalized label is removed by washing and trypsin treatment. The residual radioactivity represents trapped label and can be used to measure the extent of membrane internalization. Using this method, it was found that in addition to primaquine, a group of membrane-active drugs, specifically hydrocortisone, vinblastine, and chlorpromazine can induce membrane internalization in erythrocytes. This is a metabolic process dependent on drug concentration, temperature, and pH. Vacuole formation by all agents tested can be blocked by prior depletion of endogenous substrates or by poisoning the erythrocytes with sodium fluoride and sulfhydryl blocking agents. This phenomenon resembles in some respects the previously reported membrane internalization of energized erythrocyte ghosts. It is suggested that membrane internalization is dependent on an ATP-energized state and is influenced by the balance between the concentrations of magnesium and calcium in the membrane. This study provides a basis for proposing a unifying concept of the action of some membrane-active drugs, and for considering the role of erythrocyte membrane internalization in pathophysiologic events. Images PMID:4555785

  13. Permeability of blood-brain barrier in macaque model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson disease.

    PubMed

    Thiollier, Thibaud; Wu, Caisheng; Contamin, Hugues; Li, Qin; Zhang, Jinlan; Bezard, Erwan

    2016-06-01

    Brain bioavailability of drugs developed to address central nervous system diseases is classically documented through cerebrospinal fluid collected in normal animals, i.e., through an approximation as there are fundamental differences between cerebrospinal fluid and tissue contents. The fact that disease might affect brain availability of drugs is almost never considered at this stage although several conditions are associated with blood-brain barrier damage. Building upon our expertise in Parkinson's disease translational research, the present study addressed this gap comparing plasma and cerebrospinal fluid bioavailability of l-3,4-dihydroxyphenylalanine, carbamazepine, quinidine, lovastatin, and simvastatin, in healthy and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated macaques, the gold standard model of Parkinson's disease. The drugs were selected based upon their differential transport across the blood-brain barrier. Interestingly, brain bioavailability of quinidine was decreased while others were unaffected. Pharmacokinetics and pharmacodynamics experiments of drugs addressing Parkinson's disease might thus be performed in healthy animals unless the drugs are known to interact with the organic cation transporter. Synapse 70:231-239, 2016. © 2016 Wiley Periodicals, Inc. PMID:26799359

  14. Intrastriatal GDNF gene transfer by inducible lentivirus vectors protects dopaminergic neurons in a rat model of parkinsonism.

    PubMed

    Chen, Sha-Sha; Yang, Chun; Hao, Fei; Li, Chen; Lu, Tao; Zhao, Li-Ru; Duan, Wei-Ming

    2014-11-01

    Glial cell line-derived neurotrophic factor (GDNF) has neuroprotective effects on dopaminergic (DA) neurons both in vivo and in vitro. However, substantial evidence has shown that a long-term overexpression of GDNF gene is often associated with side effects. We previously improved tetracycline (Tet)-On lentivirus system carrying human GDNF (hGDNF) gene, and demonstrated that hGDNF gene expression was tightly regulated and functional in vitro. Here we further examined the efficiency and neuroprotection of Tet-On lentivirus-mediated hGDNF gene regulation in neural progenitor cells (NPCs) and a rat model of parkinsonism. The results showed that hGDNF gene expression was tightly regulated in transduced NPCs. Doxycycline (Dox)-induced hGDNF protected DA neurons from 6-hydroxydopamine (6-OHDA)-induced toxicity in vitro. Intrastriatal injections of Tet-On lentivirus vectors resulted in dramatically increased levels of hGDNF protein in the striatum of rats with Dox-drinking water, when compared to lentivirus-injected and saline-injected rats with normal drinking water, respectively. In addition, hGDNF protected nigral DA neurons and striatal DA fibers, and attenuated d-amphetamine-induced rotational asymmetry in the 6-OHDA lesioned rats. To the best of our knowledge, this is the first report that hGDNF gene transfer by Tet-On lentivirus vectors is tightly regulated in rat brain, and Dox-induced hGDNF is functional in neuroprotection of nigral DA neurons in a rat model of parkinsonism. PMID:24997241

  15. Drug-induced spatial dispersion of repolarization

    PubMed Central

    Antzelevitch, Charles

    2008-01-01

    Spatial dispersion of repolarization in the form of transmural, trans-septal and apico-basal dispersion of repolarization creates voltage gradients that inscribe the J wave and T wave of the ECG. Amplification of this spatial dispersion of repolarization (SDR) underlies the development of life-threatening ventricular arrhythmias associated with inherited or acquired ion channelopathies giving rise to the long QT, short QT and Brugada syndromes (BrS). This review focuses on the role of spatial dispersion of repolarization in drug-induced arrhythmogenesis associated with the long QT and BrS. In the long QT syndrome, drug-induced amplification of SDR is often secondary to preferential prolongation of the action potential duration (APD) of M cells, whereas in the BrS, it is thought to be due to selective abbreviation of the APD of right ventricular epicardium. Among the challenges ahead is the identification of a means to quantitate SDR non-invasively. This review also discusses the value of the interval between the peak and end of the T wave (Tpeak–Tend, Tp–Te) as an index of SDR and transmural dispersion of repolarization, in particular. PMID:18651395

  16. Anticancer drug-induced kidney disorders.

    PubMed

    Kintzel, P E

    2001-01-01

    Nephrotoxicity is an inherent adverse effect of certain anticancer drugs. Renal dysfunction can be categorised as prerenal uraemia, intrinsic damage or postrenal uraemia according to the underlying pathophysiological process. Renal hypoperfusion promulgates prerenal uraemia. Intrinsic renal damage results from prolonged hypoperfusion, exposure to exogenous or endogenous nephrotoxins, renotubular precipitation of xenobiotics or endogenous compounds, renovascular obstruction, glomerular disease, renal microvascular damage or disease, and tubulointerstitial damage or disease. Postrenal uraemia is a consequence of clinically significant urinary tract obstruction. Clinical signs of nephrotoxicity and methods used to assess renal function are discussed. Mechanisms of chemotherapy-induced renal dysfunction generally include damage to vasculature or structures of the kidneys, haemolytic uraemic syndrome and prerenal perfusion deficits. Patients with cancer are frequently at risk of renal impairment secondary to disease-related and iatrogenic causes. This article reviews the incidence, presentation, prevention and management of anticancer drug-induced renal dysfunction. Dose-related nephrotoxicity subsequent to administration of certain chloroethylnitrosourea compounds (carmustine, semustine and streptozocin) is commonly heralded by increased serum creatinine levels, uraemia and proteinuria. Additional signs of streptozocin-induced nephrotoxicity include hypophosphataemia, hypokalaemia, hypouricaemia, renal tubular acidosis, glucosuria, aceturia and aminoaciduria. Cisplatin and carboplatin cause dose-related renal dysfunction. In addition to increased serum creatinine levels and uraemia, electrolyte abnormalities, such as hypomagnesaemia and hypokalaemia, are commonly reported adverse effects. Rarely, cisplatin has been implicated as the underlying cause of haemolytic uraemic syndrome. Pharmaceutical antidotes to cisplatin-induced nephrotoxicity include amifostine, sodium

  17. Prediction of drug-induced catalepsy based on dopamine D1, D2, and muscarinic acetylcholine receptor occupancies.

    PubMed

    Haraguchi, K; Ito, K; Kotaki, H; Sawada, Y; Iga, T

    1997-06-01

    It is known that catalepsy serves as an experimental animal model of parkinsonism. In this study, the relationship between in vivo dopamine D1 and D2 receptor occupancies and catalepsy was investigated to predict the intensity of catalepsy induced by drugs that bind to D1 and D2 receptors nonselectively. 3H-SCH23390 and 3H-raclopride were used for the labeling of D1 and D2 receptors, respectively. The ternary complex model consisting of agonist or antagonist, receptor, and transducer was developed, and the dynamic parameters were determined. After coadministration of SCH23390 and nemonapride, catalepsy was stronger than sum of the values predicted by single administration of each drug, and it was intensified synergistically. This finding suggested the existence of interaction between D1 and D2 receptors, and the necessity for constructing the model including this interaction. To examine the validity of this model, catalepsy and in vivo dopamine receptor occupancy were measured after administration of drugs that induce or have a possibility to induce parkinsonism (haloperidol, flunarizine, manidipine, oxatomide, hydroxyzine, meclizine, and homochlorcycilzine). All of the tested drugs blocked both dopamine D1 and D2 receptors. Intensity of catalepsy was predicted with this dynamic model and was compared with the observed values. In contrast with haloperidol, flunarizine, manidipine, and oxatomide (which induced catalepsy), hydroxyzine, meclizine, and homochlorcyclizine failed to induce catalepsy. Intensities of catalepsy predicted with this dynamic model considering the interaction between D1 and D2 receptors overestimated the observed values, suggesting that these drugs have catalepsy-reducing properties as well. Because muscarinic acetylcholine (mACh) receptor antagonists inhibit the induction of catalepsy, the anticholinergic activities of the drugs were investigated. After SCH23390, nemonapride and scopolamine were administered simultaneously; catalepsy and in

  18. Novel P-TEN-induced putative kinase 1 (PINK1) variant in Indian Parkinson's disease patient.

    PubMed

    Halder, Tamali; Raj, Janak; Sharma, Vivek; Das, Parimal

    2015-09-25

    Loss-of-function mutation in PINK1 is known for causing autosomal recessive early onset Parkinsonism accounting approximately 6.5% of PD cases. Recently, PINK1 has also been shown to cause Parkinson's disease (PD) in eastern India. Present study is aimed to see its contribution in north-Indian PD patients. A total of 106 PD patients and 60 ethnically matched healthy controls were included in the study. All the patients were screened for mutation in PINK1 by direct DNA sequence analysis of the PCR amplicons covering all exons and exon-intron boundaries. Identified novel variant was reconfirmed by DNA sequencing of 10 randomly selected TA clones containing the variant amplicon. In vitro functional assay of the mutant protein was performed by transfecting COS-7 cell line with wild type and mutant (created by site-directed-mutagenesis) cDNA construct of PINK1 fused to N' terminal GFP followed by western blot analysis. Two potentially pathogenic, one being novel (p.Q267X) and 6 other apparently non-pathogenic variants were identified. Western blot analysis reveals production of truncated PINK1 fusion protein of ∼55kDa in p.Q267X mutant instead of 82/93kDa of wild type PINK1 fusion protein (molecular weight of GFP is ∼27kDa). Our study concludes that PINK1 variants are prevalent for causing Parkinson's disease (PD) in India, as revealed by the occurrence of 1.8% (2/106) in PD patients from north Indian population. The novel homozygous variant of PINK1 (c.799C>T) reported here is the plausible cause for disease manifestation in this patient. Future study, however, would be helpful to understand the functional mechanism how this premature PINK1 protein (p.Q267X) responds to cellular stress leading to the PD pathophysiology. PMID:26282903

  19. Drug-induced immune hemolytic anemia

    MedlinePlus

    Immune hemolytic anemia secondary to drugs; Anemia - immune hemolytic - secondary to drugs ... Drugs that can cause this type of hemolytic anemia include: Cephalosporins (a class of antibiotics), most common ...

  20. Drug-induced immune hemolytic anemia

    MedlinePlus

    Immune hemolytic anemia secondary to drugs; Anemia - immune hemolytic - secondary to drugs ... In some cases, a drug can cause the immune system to mistake your own red blood cells for foreign substances. The body responds by making ...

  1. Follow-up of patients affected by manganese-induced Parkinsonism after treatment with CaNa2EDTA.

    PubMed

    Herrero Hernandez, Elena; Discalzi, Gianluigi; Valentini, Consuelo; Venturi, Fabrizio; Chiò, Adriano; Carmellino, Caterina; Rossi, Luigi; Sacchetti, Anna; Pira, Enrico

    2006-05-01

    In the period of 1998-2004, seven workers affected by manganese-induced Parkinsonism were diagnosed, studied and treated with CaNa2EDTA at our Occupational Health Ward. Biological markers, as well as magnetic resonance imaging and clinical examinations, were used to assess the disease trend. Those workers still employed were immediately removed from exposure. Our results seem to confirm that very good clinical, biological and neuroradiological results can be obtained by timely removal from exposure and chelating treatment, and that amelioration can persist in time. Manganism is, however, a severe condition that can also progress independent of further exposure. Therefore, chelating treatment can be a great aid in overt manganism, but particular attention must be paid to primary prevention, as this disease should now be totally preventable and definitely merits eradication. PMID:16271769

  2. Biochanin A protects dopaminergic neurons against lipopolysaccharide-induced damage and oxidative stress in a rat model of Parkinson's disease.

    PubMed

    Wang, Jun; He, Can; Wu, Wang-Yang; Chen, Feng; Wu, Yang-Yang; Li, Wei-Zu; Chen, Han-Qing; Yin, Yan-Yan

    2015-11-01

    Parkinson's disease (PD) is the second most common neurodegenerative disease, which is characterized by loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Accumulated evidences have suggested that oxidative stress is closely associated with the dopaminergic neurodegeneration of PD that can be protected by antioxidants. Biochanin A that is an O-methylated isoflavone in chickpea is investigated to explore its protective mechanism on dopaminergic neurons of the unilateral lipopolysaccharide (LPS)-injected rat. The results showed that biochanin A significantly improved the animal model's behavioral symptoms, prevented the loss of dopaminergic neurons and inhibited the deleterious microglia activation in the LPS-induced rats. Moreover, biochanin A inhibited nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) activation and malondialdehyde (MDA) production, increased superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in the rat brain. These results suggested that biochanin A might be a natural candidate with protective properties on dopaminergic neurons against the PD. PMID:26394281

  3. Research challenges for drug-induced birth defects.

    PubMed

    Mitchell, A A

    2016-07-01

    Drug-induced birth defects (teratogenesis) represent unique adverse drug reactions (ADRs). Not only is the ADR manifest in a subject other than the one for whom treatment is intended, but most teratogens can be identified only after a drug is marketed. We know little about fetal safety for most marketed drugs, and identification of potential teratogens uniquely requires that study designs consider issues related to the effects of specific drugs, specific defects, and specific gestational timing. PMID:27037730

  4. Neuroprotective Effects of a Standardized Flavonoid Extract from Safflower against a Rotenone-Induced Rat Model of Parkinson's Disease.

    PubMed

    Ablat, Nuramatjan; Lv, Deyong; Ren, Rutong; Xiaokaiti, Yilixiati; Ma, Xiang; Zhao, Xin; Sun, Yi; Lei, Hui; Xu, Jiamin; Ma, Yingcong; Qi, Xianrong; Ye, Min; Xu, Feng; Han, Hongbin; Pu, Xiaoping

    2016-01-01

    Parkinson's disease (PD) is a major age-related neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra par compacta (SNpc). Rotenone is a neurotoxin that is routinely used to model PD to aid in understanding the mechanisms of neuronal death. Safflower (Carthamus tinctorius. L.) has long been used to treat cerebrovascular diseases in China. This plant contains flavonoids, which have been reported to be effective in models of neurodegenerative disease. We previously reported that kaempferol derivatives from safflower could bind DJ-1, a protein associated with PD, and that a flavonoid extract from safflower exhibited neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of PD. In this study, a standardized safflower flavonoid extract (SAFE) was isolated from safflower and found to primarily contain flavonoids. The aim of the current study was to confirm the neuroprotective effects of SAFE in rotenone-induced Parkinson rats. The results showed that SAFE treatment increased body weight and improved rearing behavior and grip strength. SAFE (35 or 70 mg/kg/day) treatment reversed the decreased protein expression of tyrosine hydroxylase, dopamine transporter and DJ-1 and increased the levels of dopamine and its metabolite. In contrast, acetylcholine levels were decreased. SAFE treatment also led to partial inhibition of PD-associated changes in extracellular space diffusion parameters. These changes were detected using a magnetic resonance imaging (MRI) tracer-based method, which provides novel information regarding neuronal loss and astrocyte activation. Thus, our results indicate that SAFE represents a potential therapeutic herbal treatment for PD. PMID:27563865

  5. Systems biology analysis of the proteomic alterations induced by MPP+, a Parkinson's disease-related mitochondrial toxin

    PubMed Central

    Monti, Chiara; Bondi, Heather; Urbani, Andrea; Fasano, Mauro; Alberio, Tiziana

    2015-01-01

    Parkinson's disease (PD) is a complex neurodegenerative disease whose etiology has not been completely characterized. Many cellular processes have been proposed to play a role in the neuronal damage and loss: defects in the proteosomal activity, altered protein processing, increased reactive oxygen species burden. Among them, the involvement of a decreased activity and an altered disposal of mitochondria is becoming more and more evident. The mitochondrial toxin 1-methyl-4-phenylpyridinium (MPP+), an inhibitor of complex I, has been widely used to reproduce biochemical alterations linked to PD in vitro and its precursor, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP), to induce a Parkinson-like syndrome in vivo. Therefore, we performed a meta-analysis of the literature of all the proteomic investigations of neuronal alterations due to MPP+ treatment and compared it with our results obtained with a mitochondrial proteomic analysis of SH-SY5Y cells treated with MPP+. By using open-source bioinformatics tools, we identified the biochemical pathways and the molecular functions mostly affected by MPP+, i.e., ATP production, the mitochondrial unfolded stress response, apoptosis, autophagy, and, most importantly, the synapse funcionality. Eventually, we generated protein networks, based on physical or functional interactions, to highlight the relationships among the molecular actors involved. In particular, we identified the mitochondrial protein HSP60 as the central hub in the protein-protein interaction network. As a whole, this analysis clarified the cellular responses to MPP+, the specific mitochondrial proteome alterations induced and how this toxic model can recapitulate some pathogenetic events of PD. PMID:25698928

  6. An update on risk factors for drug-induced arrhythmias.

    PubMed

    Vlachos, Konstantinos; Georgopoulos, Stamatis; Efremidis, Michael; Sideris, Antonios; Letsas, Konstantinos P

    2016-01-01

    A variety of drugs, either anti-arrhythmics or non-antiarrhythmics, have been associated with drug-induced arrhythmias. Drug-induced arrhythmias are usually observed in the presence of long QT interval or Brugada electrocardiographic pattern. Clinical risk factors, such as female gender, structural heart disease, metabolic and electrolyte abnormalities, bradycardia and conduction disease, increased drug bioavailability, and silent channelopathies act as ''effect amplifiers'' which can make an otherwise relatively safe drug dangerous with regard to risk for polymorphic ventricular tachycardia in the setting of QT interval prolongation. A drug-induced type 1 electrocardiographic pattern of Brugada syndrome is considered highly proarrhythmic. Specific electrocardiographic markers including the corrected QT interval, QRS duration, Tpeak-Tend/QT ratio, and others may predict the risk of arrhythmias in both situations. The present review highlights on the current clinical and electrocardiographic risk factors for prediction of drug-induced arrhythmias. PMID:26460585

  7. Drug-induced lupus erythematosus: incidence, management and prevention.

    PubMed

    Chang, Christopher; Gershwin, M Eric

    2011-05-01

    The generation of autoantibodies and autoimmune diseases such as systemic lupus erythematosus has been associated with the use of certain drugs in humans. Early reports suggested that procainamide and hydralazine were associated with the highest risk of developing lupus, quinidine with a moderate risk and all other drugs were considered low or very low risk. More recently, drug-induced lupus has been associated with the use of the newer biological modulators such as tumour necrosis factor (TNF)-α inhibitors and interferons. The clinical features and laboratory findings of TNFα inhibitor-induced lupus are different from that of traditional drug-induced lupus or idiopathic lupus, and standardized criteria for the diagnosis of drug-induced lupus have not been established. The mechanism(s) responsible for the development of drug-induced lupus may vary depending on the drug or even on the patient. Besides lupus, other autoimmune diseases have been associated with drugs or toxins. Diagnosis of drug-induced lupus requires identification of a temporal relationship between drug administration and symptom development, and in traditional drug-induced lupus there must be no pre-existing lupus. Resolution of symptoms generally occurs after cessation of the drug. In this review, we will discuss those drugs that are more commonly associated with drug-induced lupus, with an emphasis on the new biologicals and the difficulty of making the diagnosis of drug-induced lupus against a backdrop of the autoimmune diseases that these drugs are used to treat. Stimulation of the immune system by these drugs to cause autoimmunity may in fact be associated with an increased effectiveness in treating the pathology for which they are prescribed, leading to the dilemma of deciding which is worse, the original disease or the adverse effect of the drug. Optimistically, one must hope that ongoing research in drug development and in pharmacogenetics will help to treat patients with the maximum

  8. Myalgias and Myopathies: Drug-Induced Myalgias and Myopathies.

    PubMed

    Holder, Kathryn

    2016-01-01

    Drugs can cause myalgias and myopathies through a variety of mechanisms. Most drug-induced myopathies are potentially reversible if recognized early. Prescribers should be familiar with common drug-induced myopathies and drug-drug interactions. Clinical presentations can be subacute or acute, ranging from benign muscle pain with mild elevations of serum creatine kinase to fulminant rhabdomyolysis with high creatine kinase levels and potentially life-threatening acute kidney injury. Myalgias and proximal muscle weakness are typical symptoms; onset can be weeks to months after drug exposure. Endocrine disorders and inflammatory etiologies should be excluded because their management may differ from that of drug-induced myopathies. Statin drugs are prescribed widely, and statin-induced myopathy is one of the most commonly recognized and studied myopathies. Risk factors include dose and type of statin prescribed, older age, female sex, genetic predisposition, and concomitant use of other drugs metabolized by the cytochrome P450 system. Glucocorticoids, immunologic drugs, and antimicrobials, as well as other drugs and alcohol, can cause myopathies. Management typically involves discontinuing the drug and switching to an alternative drug or considering an alternative dosing schedule. Referral to a neuromuscular subspecialist is warranted if symptoms persist. PMID:26734833

  9. Baicalein antagonizes rotenone-induced apoptosis in dopaminergic SH-SY5Y cells related to Parkinsonism

    PubMed Central

    2012-01-01

    Background Two active compounds, baicalein and its glycoside baicalin were found in the dried root of Scutellaria baicalensis Georgi, and reported to be neuroprotective in vitro and in vivo. This study aims to evaluate the protective effects of baicalein on the rotenone-induced apoptosis in dopaminergic SH-SY5Y cells related to parkinsonism. Methods Cell viability and cytotoxicity were determined by MTT assay. The degree of nuclear apoptosis was evaluated with a fluorescent DNA-binding probe Hoechst 33258. The production of reactive oxidative species (ROS) and loss of mitochondrial membrane potential (ΔΨm) were determined by fluorescent staining with DCFH-DA and Rhodanmine 123, respectively. The expression of Bax, Bcl-2, cleaved caspase-3 and phosphorylated ERK1/2 was determined by the Western blots. Results Baicalein significantly increased viability and decreased rotenone-induced death of SH-SY5Y cells in a dose-dependent manner. Pre- and subsequent co-treatment with baicalein preserved the cell morphology and attenuated the nuclear apoptotic characteristics triggered by rotenone. Baicalein antagonized rotenone-induced overproduction of ROS, loss of ΔΨm, the increased expression of Bax, cleaved caspase-3 and phosphorylated ERK1/2 and the decreased expression of Bcl-2. Conclusion The antioxidative effect, mitochondrial protection and modulation of anti-and pro-apoptotic proteins are related to the neuroprotective effects of baicalein against rotenone induced cell death in SH-SY5Y cells. PMID:22264378

  10. The Neuroprotective Role of Insulin Against MPP(+) -Induced Parkinson's Disease in Differentiated SH-SY5Y Cells.

    PubMed

    Ramalingam, Mahesh; Kim, Sung-Jin

    2016-04-01

    Parkinson's disease (PD) is a common chronic neurodegenerative disorder associated with aging that primarily caused by the death of dopaminergic neurons in the substantia nigra pars compacta (SN). Retinoic acid (RA)-differentiated human neuroblastoma SH-SY5Y cells (SH-SY5Y+RA) have been broadly utilized in studies of mechanisms of the pathogenesis underlying 1-Methyl-4-phenyl pyridinium (MPP(+) )-induced PD models. Here, we investigated the neuroprotective mechanisms of insulin on MPP(+) -induced neurotoxicity on SH-SY5Y+RA cells. Recent studies suggest that insulin has a protective effect against oxidative stress but not been elucidated for PD. In this study, pretreatment of insulin prevented the cell death in a dose dependent manner and lowered nitric oxide (NO) release, reactive oxygen species (ROS), and calcium ion (Ca(2+) ) influx induced by MPP(+) . Insulin also elevated tyrosine hydroxylase (TH) and insulin signaling pathways in dopaminergic neuron through activating PI3K/Akt/GSK-3 survival pathways which in turn inhibits MPP(+) -induced iNOS and ERK activation, and Bax to Bcl-2 ratio. These results suggest that insulin has a protective effect on MPP(+) -neurotoxicity in SH-SY5Y+RA cells. J. Cell. Biochem. 117: 917-926, 2016. © 2015 Wiley Periodicals, Inc. PMID:26364587

  11. Side effect profile of 5-HT treatments for Parkinson's disease and L-DOPA-induced dyskinesia in rats

    PubMed Central

    Lindenbach, D; Palumbo, N; Ostock, C Y; Vilceus, N; Conti, M M; Bishop, C

    2015-01-01

    BACKGROUND AND PURPOSE Treatment of Parkinson's disease (PD) with L-DOPA eventually causes abnormal involuntary movements known as dyskinesias in most patients. Dyskinesia can be reduced using compounds that act as direct or indirect agonists of the 5-HT1A receptor, but these drugs have been reported to worsen PD features and are known to produce ‘5-HT syndrome’, symptoms of which include tremor, myoclonus, rigidity and hyper-reflexia. EXPERIMENTAL APPROACH Sprague-Dawley rats were given unilateral nigrostriatal dopamine lesions with 6-hydroxydopamine. Each of the following three purportedly anti-dyskinetic 5-HT compounds were administered 15 min before L-DOPA: the full 5-HT1A agonist ±-8-hydroxy-2-dipropylaminotetralin (±8-OH-DPAT), the partial 5-HT1A agonist buspirone or the 5-HT transporter inhibitor citalopram. After these injections, animals were monitored for dyskinesia, 5-HT syndrome, motor activity and PD akinesia. KEY RESULTS Each 5-HT drug dose-dependently reduced dyskinesia by relatively equal amounts (±8-OH-DPAT ≥ citalopram ≥ buspirone), but 5-HT syndrome was higher with ±8-OH-DPAT, lower with buspirone and not present with citalopram. Importantly, with or without L-DOPA, all three compounds provided an additional improvement of PD akinesia. All drugs tempered the locomotor response to L-DOPA suggesting dyskinesia reduction, but vertical rearing was reduced with 5-HT drugs, potentially reflecting features of 5-HT syndrome. CONCLUSIONS AND IMPLICATIONS The results suggest that compounds that indirectly facilitate 5-HT1A receptor activation, such as citalopram, may be more effective therapeutics than direct 5-HT1A receptor agonists because they exhibit similar anti-dyskinesia efficacy, while possessing a reduced side effect profile. PMID:25175895

  12. The use of nanopore analysis for discovering drugs which bind to α-synuclein for treatment of Parkinson's disease.

    PubMed

    Tavassoly, Omid; Kakish, Joe; Nokhrin, Sergiy; Dmitriev, Oleg; Lee, Jeremy S

    2014-12-17

    A major feature of Parkinson's disease is the formation of Lewy bodies in dopaminergic neurons which consist of misfolded α-synuclein. The binding of natural products to α-synuclein was evaluated by nanopore analysis and caffeine, curcumin, and nicotine all caused large conformational changes which may be related to their known neuroprotective effect in Parkinson's disease. The binding of the stereoisomers of nicotine were also studied by ITC, CD and NMR. It is proposed that (-)-nicotine causes the folding of α-synuclein into a loop with interaction between the N- and C-termini. For (+)-nicotine the binding is weaker and mainly involves residues in the N-terminus. Caffeine and nicotine can bind to α-synuclein simultaneously and may provide lead structures for the development of other compounds for the treatment of PD. PMID:25081642

  13. Clinical and endoscopic characteristics of drug-induced esophagitis

    PubMed Central

    Kim, Su Hwan; Jeong, Ji Bong; Kim, Ji Won; Koh, Seong-Joon; Kim, Byeong Gwan; Lee, Kook Lae; Chang, Mee Soo; Im, Jong Pil; Kang, Hyoun Woo; Shin, Cheol Min

    2014-01-01

    AIM: To investigate clinical, endoscopic and pathological characteristics of drug-induced esophagitis. METHODS: Data for patients diagnosed with drug-induced esophagitis from April 2002 to May 2013 was reviewed. Patients diagnosed with malignancy, viral or fungal esophagitis were excluded. Clinical, endoscopic and pathological characteristics of patients diagnosed with drug-induced esophagitis were analyzed. RESULTS: Seventy-eight patients were diagnosed with drug-induced esophagitis. Their mean age was 43.9 ± 18.9 years and 35.9% were male. Common symptoms were chest pain (71.8%), odynophagia (38.5%) and dysphagia (29.5%). The endoscopic location was in the middle third of esophagus in 78.2%. Endoscopic findings were ulcer (82.1%), erosion (17.9%), ulcer with bleeding (24.4%), coating with drug material (5.1%), impacted pill fragments (3.8%) and stricture (2.6%). Kissing ulcers were observed in 43.6%. The main causative agents were antibiotics and non-steroidal anti-inflammatory drugs. All the patients were treated with proton pump inhibitors (PPIs) or sucralfate, and the causative drugs were discontinued. Nineteen patients with drug-induced esophagitis were followed up with endoscopy and revealed normal findings, scars or healing ulcers. CONCLUSION: Drug-induced esophagitis mainly presents as chest pain, odynophagia and dysphagia, and may be successfully treated with PPIs and discontinuation of the causative drug. Kissing ulcers were observed in 43.6%. PMID:25152603

  14. Drug-Induced Glomerular Disease: Immune-Mediated Injury

    PubMed Central

    Markowitz, Glen S.; Radhakrishnan, Jai

    2015-01-01

    Drug-induced autoimmune disease was initially described decades ago, with reports of vasculitis and a lupus-like syndrome in patients taking hydralazine, procainamide, and sulfadiazine. Over the years, multiple other agents have been linked to immune-mediated glomerular disease, often with associated autoantibody formation. Certain clinical and laboratory features may distinguish these entities from their idiopathic counterparts, and making this distinction is important in the diagnosis and management of these patients. Here, drug-induced, ANCA-associated vasculitis, drug-induced lupus, and drug-associated membranous nephropathy are reviewed. PMID:26092827

  15. Mechanisms of drug-induced proarrhythmia in clinical practice

    PubMed Central

    Konstantopoulou, Arkadia; Tsikrikas, Spyros; Asvestas, Dimitrios; Korantzopoulos, Panagiotis; Letsas, Konstantinos P

    2013-01-01

    Drug-induced proarrhythmia represents a great challenge for those involved in the development of novel pharmaceuticals and in the regulatory bodies for drug approval as well as for the prescribing clinicians. Our understanding of the mechanisms that underlie drug-induced proarrhythmia has grown dramatically over the last two decades. A growing number of cardiac and non-cardiac agents have been shown to alter cardiac repolarization predisposing to fatal cardiac arrhythmias such as ventricular tachycardia or ventricular fibrillation and sudden cardiac death. These agents may induce the phenotype of long QT syndrome and less commonly of short QT syndrome and Brugada syndrome (BS). Although, genetic susceptibility underlie drug-induced proarrhythmia in certain cases, current data are limited regarding this topic. The present review surveys the current published literature on the mechanisms and the offending medical agents that predispose to drug-induced long QT syndrome, short QT syndrome and BS. Drug-induced proarrhythmia should be considered as a predictor of sudden cardiac death and should prompt critical re-evaluation of the risks and benefits of the suspicious medication. Survivors of drug-induced proarrhythmia and family members require careful examination and possibly genetic testing for the presence of a channelopathy. Treating physicians are advised to follow the lists of agents implicated in drug-induced proarrhythmia in order to minimize the risk of arrhythmia and sudden cardiac death. PMID:23847724

  16. Atomistic Investigation of Cu-Induced Misfolding in the Onset of Parkinson's Disease

    NASA Astrophysics Data System (ADS)

    Rose, Francis; Hodak, Miroslav; Bernholc, Jerry

    2009-03-01

    A nucleation mechanism for the misfolding of α-synuclein, the protein implicated in Parkinson's Disease (PD), is investigated using computer simulations. Through a combination of ab initio and classical simulation techniques, the conformational evolution of copper-ion-initiated misfolding of α-synuclein is determined. Based on these investigations and available experimental evidence, an atomistic model detailing the nucleation-initiated pathogenesis of PD is proposed. Once misfolded, the proteins can assemble into fibrils, the primary structural components of the deleterious PD plaques. Our model identifies a process of structural modifications to an initially unfolded α-synuclein that results in a partially folded intermediate with a well defined nucleation site as a precursor to the fully misfolded protein. The identified pathway can enable studies of reversal mechanisms and inhibitory agents, potentially leading to the development of effective therapies.

  17. Unraveling Parkinson's: Three Clues

    MedlinePlus

    ... Bar Home Current Issue Past Issues Unraveling Parkinson's: Three Clues Past Issues / Summer 2006 Table of Contents ... Dream Robber: Living with Parkinson's disease / Unraveling Parkinson's: Three Clues / Parkinson's Disease: The Newest Advances Summer 2006 ...

  18. Myeloid cell leukemia 1 (Mcl(-1)) protects against 1-methyl-4-phenylpyridinium ion (MPP+) induced apoptosis in Parkinson's disease.

    PubMed

    Fan, Lijing; Jiang, Li; Du, Zhongde

    2015-10-01

    The myeloid cell leukemia 1 (Mcl(-1)) is an anti-apoptotic member of the Bcl-2 family, which plays an essential role in protecting cells against apoptosis. The expression pattern and potential roles of Mcl(-1) in Parkinson's diseases (PD) are still unknown. In this study, our results indicated that 1-methyl-4-phenylpyridinium (MPP+) treatment augmented the expression of Mcl(-1) at both messenger RNA (mRNA) and protein levels in a dose-dependent manner in SH-SY5Y cells. Moreover, we observed increased phosphorylation of Elk-1at Ser383 as well as nuclear translocation of Elk-1 in exposure to MPP+ treatment. Importantly, the elevated expression of Mcl(-1) induced by MPP+ was abolished by knockdown of Elk-1. It was also found that inhibition of Mcl(-1) by small RNA transfection exacerbates MPP + -induced LDH release after 48 h incubation. In addition, Hoechst 33,258 nuclear staining results demonstrated that silence of Mcl(-1) induced a significant increase in apoptosis in cells when compared with the control condition. Mechanistically, the levels of cleaved Caspase3 and PARP were elevated in MPP+ treated cells, which was exacerbated by knockdown of Mcl(-1). These findings suggest that Mcl(-1) might be a potential therapeutic target for PD treatment. PMID:26264181

  19. Lanosterol induces mitochondrial uncoupling and protects dopaminergic neurons from cell death in a model for Parkinson's disease

    PubMed Central

    Lim, L; Jackson-Lewis, V; Wong, L C; Shui, G H; Goh, A X H; Kesavapany, S; Jenner, A M; Fivaz, M; Przedborski, S; Wenk, M R

    2012-01-01

    Parkinson's disease (PD) is a neurodegenerative disorder marked by the selective degeneration of dopaminergic neurons in the nigrostriatal pathway. Several lines of evidence indicate that mitochondrial dysfunction contributes to its etiology. Other studies have suggested that alterations in sterol homeostasis correlate with increased risk for PD. Whether these observations are functionally related is, however, unknown. In this study, we used a toxin-induced mouse model of PD and measured levels of nine sterol intermediates. We found that lanosterol is significantly (∼50%) and specifically reduced in the nigrostriatal regions of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice, indicative of altered lanosterol metabolism during PD pathogenesis. Remarkably, exogenous addition of lanosterol rescued dopaminergic neurons from 1-methyl-4-phenylpyridinium (MPP+)-induced cell death in culture. Furthermore, we observed a marked redistribution of lanosterol synthase from the endoplasmic reticulum to mitochondria in dopaminergic neurons exposed to MPP+, suggesting that lanosterol might exert its survival effect by regulating mitochondrial function. Consistent with this model, we find that lanosterol induces mild depolarization of mitochondria and promotes autophagy. Collectively, our results highlight a novel sterol-based neuroprotective mechanism with direct relevance to PD. PMID:21818119

  20. Inhibition of Drp1 mitochondrial translocation provides neural protection in dopaminergic system in a Parkinson's disease model induced by MPTP.

    PubMed

    Filichia, Emily; Hoffer, Barry; Qi, Xin; Luo, Yu

    2016-01-01

    Accumulating evidence suggest mitochondria-mediated pathways play an important role in dopaminergic neuronal cell death in Parkinson's disease (PD). Drp1, a key regulator of mitochondrial fission, has been shown to be activated and translocated to mitochondria under stress, leading to excessive mitochondria fission and dopaminergic neuronal death in vitro. However, whether Drp1 inhibition can lead to long term stable preservation of dopaminergic neurons in PD-related mouse models remains unknown. In this study, using a classical MPTP animal PD model, we showed for the first time Drp1 activation and mitochondrial translocation in vivo after MPTP administration. Inhibition of Drp1 activation by a selective peptide inhibitor P110, blocked MPTP-induced Drp1 mitochondrial translocation and attenuated dopaminergic neuronal loss, dopaminergic nerve terminal damage and behavioral deficits caused by MPTP. MPTP-induced microglial activation and astrogliosis were not affected by P110 treatment. Instead, inhibition of Drp1 mitochondrial translocation diminished MPTP-induced p53, BAX and PUMA mitochondrial translocation. This study demonstrates that inhibition of Drp1 hyperactivation by a Drp1 peptide inhibitor P110 is neuroprotective in a MPTP animal model. Our data also suggest that the protective effects of P110 treatment might be mediated by inhibiting the p53 mediated apoptotic pathways in neurons through inhibition of Drp1-dependent p53 mitochondrial translocation. PMID:27619562

  1. Activation of α7 nicotinic acetylcholine receptors protects astrocytes against oxidative stress-induced apoptosis: implications for Parkinson's disease.

    PubMed

    Liu, Yuan; Zeng, Xiaoning; Hui, Yujian; Zhu, Chenlei; Wu, Jie; Taylor, Devin H; Ji, Juan; Fan, Weimin; Huang, Zuhu; Hu, Jun

    2015-04-01

    Astrocytes have been implicated in the immune responses associated with Parkinson's disease (PD). Inhibition of astrocyte apoptosis is a novel strategy for the treatment of PD. Recent studies suggest that α7 nicotinic acetylcholine receptors (α7-nAChRs) expressed in glial cells are critical links between inflammation and neurodegeneration in PD. However, little is known about their contribution to astrocyte apoptosis during the development of this disorder. In the present study, we showed that nicotine exerts a protective effect on H2O2-induced astrocyte apoptosis and glial cell-derived neurotrophic factor (GDNF) downregulation, and this effect was abolished by an α7-nAChR-selective antagonist. The underlying mechanisms might involve alleviation of mitochondrial membrane potential loss, stabilization of the Bax/Bcl-2 balance, and inhibition of cleaved caspase-9 activity through α7-nAChR activation. Systemic administration of nicotine dramatically alleviated MPTP-induced symptoms, protected dopaminergic neurons against degeneration, inhibited astrocytes and microglia activation in the substantia nigra pars compacta (SNpc) and blocked the decrease of GDNF in the striatum by activating α7-nAChRs. Taken together these findings demonstrate, for the first time, that nicotine suppresses H2O2-induced astrocyte apoptosis via the mitochondrial pathway through the stimulation of α7-nAChRs. Targeting α7-nAChRs expressed in astrocytes may be a novel therapeutic strategy for the treatment of neurodegenerative disorders. PMID:25486621

  2. Protective role of SIRT5 against motor deficit and dopaminergic degeneration in MPTP-induced mice model of Parkinson's disease.

    PubMed

    Liu, Lei; Peritore, Carina; Ginsberg, Jessica; Shih, Jennifer; Arun, Siddharth; Donmez, Gizem

    2015-03-15

    Parkinson's disease (PD) is characterized by progressive loss of nigrostriatal dopaminergic neurons that results in motor deficits including resting tremor, rigidity, bradykinesia, and postural instability. Despite decades of intensive study, the underlying molecular mechanisms are not fully understood. Multiple lines of evidence indicate that mitochondrial dysfunction and oxidative stress contribute to neuronal death, which is the key feature of neurodegeneration. Mitochondria are pivotal organelles that host essential functions in neuronal viability including energy production, oxidative phosphorylation, calcium buffering, redox homeostasis and apoptosis. SIRT5, which localizes in the mitochondrial matrix, is nicotinamide adenine dinucleotide (NAD(+))-dependent histone deacetylase. The physiological and pathophysiological functions of SIRT5 in vivo remain elusive although it is known to be an important energy sensor. Here, we investigated the role of SIRT5 in the pathogenesis of PD mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We present evidence that SIRT5 deficiency, by itself, does not affect motor and non-motor functions; however, lack of SIRT5 exacerbates MPTP-induced motor deficits. Consistently, MPTP-exposed SIRT5 knockout mice exhibited more severe nigrostriatal dopaminergic degeneration than that observed in wild-type controls. Furthermore, deletion of SIRT5 leads to a larger decrease, relative to control, in the expression level of manganese superoxide dismutase (SOD2), a mitochondria-specific antioxidant enzyme, after MPTP induction. These findings indicate that SIRT5 ameliorates MPTP-induced nigrostriatal dopaminergic degeneration via preserving mitochondrial antioxidant capacity. PMID:25541039

  3. Stress-Induced Executive Dysfunction in GDNF-Deficient Mice, A Mouse Model of Parkinsonism.

    PubMed

    Buhusi, Mona; Olsen, Kaitlin; Yang, Benjamin Z; Buhusi, Catalin V

    2016-01-01

    Maladaptive reactivity to stress is linked to improper decision making, impulsivity, and discounting of delayed rewards. Chronic unpredictable stress (CUS) alters dopaminergic function, re-shapes dopaminergic circuits in key areas involved in decision making, and impairs prefrontal-cortex dependent response inhibition and working memory. Glial-derived neurotrophic factor (GDNF) is essential for regulating dopamine (DA) release in the basal ganglia and for the survival of dopaminergic neurons; GDNF-deficient mice are considered an animal model for aging-related Parkinsonism. Recently, GDNF expression in the striatum has been linked to resilience to stress. Here we investigated the effects of CUS on decision making in GDNF-heterozygous (HET) mice and their wild-type littermate controls (WT). Before CUS no differences in temporal discounting (TD) were found between genotypes. However, following CUS GDNF HET mice, having a partial reduction of GDNF levels, showed increased impulsive choice indexed by a reduction in percent Larger-Later (LL) choices in the TD paradigm, and a reduction in area under the TD curve. Moreover, stressed GDNF HET mice, but not their WT controls, showed decreased neuronal activation (number of cFos positive neurons) in the orbitofrontal cortex (OFC), nucleus accumbens (NA) core, and NA shell, suggestive of a maladaptive response to stress. Interestingly, area under the TD curve positively correlated with cFos activation in the NA core, and NA shell, but not with orbitofrontal activity. These results provide further evidence of the differential involvement of the OFC, NA core, and NA shell in impulsive choice, and identify GDNF-deficient mice as a double-hit (gene × environment) model of stress-related executive dysfunction, particularly relevant to substance abuse and Parkinson's disease (PD). PMID:27445722

  4. Adverse Outcome Pathways and Drug-Induced Liver Injury Testing.

    PubMed

    Vinken, Mathieu

    2015-07-20

    Drug-induced liver injury is a prominent reason for premarketing and postmarketing drug withdrawal and can be manifested in a number of ways, such as cholestasis, steatosis, and fibrosis. The mechanisms driving these toxicological processes have been well characterized and have been emdedded in adverse outcome pathway frameworks in recent years. This review evaluates these constructs and simultaneously illustrates their use in the preclinical testing of drug-induced liver injury. PMID:26119269

  5. Adverse outcome pathways and drug-induced liver injury testing

    PubMed Central

    Vinken, Mathieu

    2015-01-01

    Drug-induced liver injury is a prominent reason for premarketing and postmarketing drug withdrawal and can be manifested in a number of ways, such as cholestasis, steatosis and fibrosis. The mechanisms driving these toxicological processes have been well characterized and have been emdedded in adverse outcome pathway frameworks in recent years. This paper reviews these constructs and simultaneously illustrates their use in the preclinical testing of drug-induced liver injury. PMID:26119269

  6. Pathways to relapse: the neurobiology of drug- and stress-induced relapse to drug-taking.

    PubMed Central

    Stewart, J

    2000-01-01

    Relapse is a major characteristic of drug addiction, and remains the primary problem in treating drug abuse. Without an understanding of the factors that determine renewed drug-seeking, the urge to use drugs, and the persistent craving for them, it is unlikely that health care professionals can provide effective treatment. Using an animal model of relapse, the author and her team are studying factors that induce reinstatement of drug-taking behaviour after short and long periods of abstinence, and they are exploring the neurobiological basis of these effects. In their experiments, rats are trained to self-administer drugs intravenously by pressing 1 of 2 levers. During a subsequent period, the drug is no longer available, but the rats are free to try to obtain the drug (a period of "extinction training"). After extinction of responding, the investigators test for the ability of various events to reinitiate drug-seeking. On this background of renewed drug-seeking or relapse, the investigators search for pharmacological and neurochemical manipulations that might block or attenuate such behaviour. They have found that the 2 most effective events for reinstating responding after both short and long drug-free periods are re-exposure to the drug itself and exposure to a brief period of stress. The critical neurochemical pathways mediating drug-induced relapse are not identical to those mediating stress-induced relapse. Relapse induced by "priming" injections of heroin or cocaine involves activation of the mesolimbic dopaminergic pathways, whereas relapse induced by stress involves actions of corticotropin-releasing factor (CRF) in the brain, and of brain noradrenergic (NE) systems. In addition, evidence shows that CRF and NE may interact at the level of the bed nucleus of the stria terminalis in stress-induced relapse. By contrast, relapse induced by "priming" injections of drugs is relatively unaffected by manipulation of CRF and NE systems of the brain. PMID:10740986

  7. Alpha-Synuclein Oligomers Interact with Metal Ions to Induce Oxidative Stress and Neuronal Death in Parkinson's Disease

    PubMed Central

    Deas, Emma; Cremades, Nunilo; Angelova, Plamena R.; Ludtmann, Marthe H.R.; Yao, Zhi; Chen, Serene; Horrocks, Mathew H.; Banushi, Blerida; Little, Daniel; Devine, Michael J.; Gissen, Paul; Klenerman, David; Dobson, Christopher M.; Wood, Nicholas W.

    2016-01-01

    Abstract Aims: Protein aggregation and oxidative stress are both key pathogenic processes in Parkinson's disease, although the mechanism by which misfolded proteins induce oxidative stress and neuronal death remains unknown. In this study, we describe how aggregation of alpha-synuclein (α-S) from its monomeric form to its soluble oligomeric state results in aberrant free radical production and neuronal toxicity. Results: We first demonstrate excessive free radical production in a human induced pluripotent stem-derived α-S triplication model at basal levels and on application of picomolar doses of β-sheet-rich α-S oligomers. We probed the effects of different structural species of α-S in wild-type rat neuronal cultures and show that both oligomeric and fibrillar forms of α-S are capable of generating free radical production, but that only the oligomeric form results in reduction of endogenous glutathione and subsequent neuronal toxicity. We dissected the mechanism of oligomer-induced free radical production and found that it was interestingly independent of several known cellular enzymatic sources. Innovation: The oligomer-induced reactive oxygen species (ROS) production was entirely dependent on the presence of free metal ions as addition of metal chelators was able to block oligomer-induced ROS production and prevent oligomer-induced neuronal death. Conclusion: Our findings further support the causative role of soluble amyloid oligomers in triggering neurodegeneration and shed light into the mechanisms by which these species cause neuronal damage, which, we show here, can be amenable to modulation through the use of metal chelation. Antioxid. Redox Signal. 24, 376–391. PMID:26564470

  8. [THREE CASES OF DRUG-INDUCED PNEUMONIA CAUSED BY MESALAZINE].

    PubMed

    Akiyama, Norimichi; Yokomura, Koshi; Nozue, Tsuyoshi; Abe, Takefumi; Matsui, Takashi; Suda, Takafumi

    2015-12-01

    We report three cases of drug-induced pneumonia caused by mesalazine. They were all diagnosed as ulcerative colitis and treated with mesalazine orally. Our three cases and literature review revealed that mesalazine-induced pneumonia resemble like eosinophilic pneumonia or organizing pneumonia and that have good prognosis with drug cessation or administration of corticosteroid. The patient of ulcerative colitis is increasing every year and it is anticipated that the patient with mesalazine-induced pneumonia may also increase. In the treatment of ulcerative colitis with mesalazine, we should pay attention with patient's cough or fever for early detection of drug-induced pneumonia. PMID:26727138

  9. Drug-induced valvular heart disease: an update.

    PubMed

    Andrejak, Michel; Tribouilloy, Christophe

    2013-05-01

    Numerous reports have shown an unquestionable association between fibrotic valve disease and the following drugs: ergot alkaloids (such as methysergide and ergotamine), ergot-derived dopaminergic agonists (such as pergolide and cabergoline) and drugs metabolized into norfenfluramine (such as fenfluramine, dexfenfluramine and benfluorex). This review focuses on different aspects of drug-induced valvular heart disease: historical background; echocardiographic features; different drugs recognized as being responsible for valvular heart disease; and pathophysiology. PMID:23769407

  10. Parkinson disease

    MedlinePlus

    Nerve cells use a brain chemical called dopamine to help control muscle movement. With Parkinson disease, the brain cells that make dopamine slowly die. Without dopamine, the cells that control movement ...