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1.
Neth J Med ; 78(5): 282-285, 2020 09.
Article in English | MEDLINE | ID: mdl-33093253

ABSTRACT

Haemophagocytic lymphohistiocytosis (HLH) is a rare hyperinflammatory condition that can be triggered by infections, malignancies, or auto-immune diseases. Here, we present a patient with rapidly progressive HLH triggered by a herpes simplex virus type 2 (HSV-2) primary infection. The patient was successfully treated with intravenous high-dose acyclovir, immunoglobulins, and dexamethasone. This is the first report of HSV-2-associated HLH in an immunocompetent adult patient.


Subject(s)
Herpes Simplex , Lymphohistiocytosis, Hemophagocytic , Acyclovir , Adult , Herpes Simplex/complications , Herpesvirus 2, Human , Humans , Lymphohistiocytosis, Hemophagocytic/complications
2.
Ned Tijdschr Geneeskd ; 1642020 07 22.
Article in Dutch | MEDLINE | ID: mdl-32779924

ABSTRACT

Post-exposure prophylaxis (PEP) with varicella zoster immunoglobulins (VZIG) should be administered as soon as possible after exposure to the virus, but always within ten days; in the previous guidelines this was within 96 hours. In cases of perinatal exposure, PEP with VZIG should be administered to neonates if the mother develops clinical chickenpox between seven days before delivery and seven days after delivery; in the previous guidelines this was between five days before delivery and two days after delivery. A new chapter on the treatment of chickenpox has been added to the guidelines.


Subject(s)
Chickenpox/prevention & control , Herpes Zoster/prevention & control , Immune Sera/administration & dosage , Post-Exposure Prophylaxis/methods , Chickenpox/transmission , Female , Herpes Zoster/transmission , Herpesvirus 3, Human , Humans , Infant, Newborn , Male , Mothers , Practice Guidelines as Topic , Pregnancy , Risk Factors
3.
Infect Dis (Lond) ; 50(11-12): 847-852, 2018.
Article in English | MEDLINE | ID: mdl-30317893

ABSTRACT

INTRODUCTION: HIV-infected patients are more than 100-fold greater at risk for developing malignant AIDS-related lymphoma (ARL) compared to the general population. Most ARLs are EBV related. The main purpose of this study was to investigate whether a high peak EBV DNA load in HIV-infected patients is predictive of ARL, including classical Hodgkin lymphoma. METHODS: From an ongoing prospective HIV positive cohort study, we conducted a case-control study between 2004 and 2016 among patients from whom at least one EBV DNA load in serum or plasma was available. We compared peak EBV DNA load between patients with (49 cases) and without ARL (156 controls). RESULTS: The geometric mean of the peak EBV DNA load measured before diagnosis of malignant lymphoma was 52,565 IU/mL in EBER-positive lymphoma patients vs. 127 IU/mL in controls (p < .001). Patients with EBV DNA loads >100,000 IU/mL have an increased risk for diagnosis of malignant lymphoma compared to patients with EBV DNA loads ≤100,000 IU/mL (adjusted OR 12.53; 95%CI: 4.08; 38.42). In the longitudinal study, including 13 patients with at least three left-over plasma samples available for retesting, measurements of EBV-DNA during the preceding 12 months proved to be of poor value for predicting subsequent lymphoma diagnosis. CONCLUSIONS: A EBV DNA load >100,000 IU/mL can be useful in clinical setting to accelerate time to diagnosis and treatment. EBV-DNA loads in samples taken during the preceding year of ARL diagnosis showed to be of poor predictive value.


Subject(s)
DNA, Viral/blood , Epstein-Barr Virus Infections/virology , HIV Infections/complications , Herpesvirus 4, Human/isolation & purification , Lymphoma, AIDS-Related/diagnosis , Adult , Case-Control Studies , Cohort Studies , Cross-Sectional Studies , Epstein-Barr Virus Infections/complications , Female , HIV Infections/virology , Herpesvirus 4, Human/genetics , Humans , Longitudinal Studies , Lymphoma, AIDS-Related/complications , Lymphoma, AIDS-Related/virology , Male , Middle Aged , Prognosis , Prospective Studies , Risk , Viral Load
4.
J Clin Virol ; 79: 12-17, 2016 06.
Article in English | MEDLINE | ID: mdl-27045454

ABSTRACT

BACKGROUND: Rapid antigen detection tests (RADTs) are increasingly used to detect influenza viruses and respiratory syncytial virus (RSV). However, their sensitivity and specificity are a matter of debate, challenging their clinical usefulness. OBJECTIVES: Comparing diagnostic performances of BinaxNow Influenza AB(®) (BNI) and BinaxNow RSV(®) (BNR), to those of real-time reverse transcriptase PCR (RT-PCR), virus isolation and direct immunofluorescence (D-IF) in paediatric patients. STUDY DESIGN: Between November 2005 and September 2013, 521 nasal washings from symptomatic children (age <5 years) attending our tertiary care centre were tested, with a combination of the respective assays using RT-PCR as gold standard. RESULTS: Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of BNI were 69% (confidence interval [CI] [51-83]), 96% [94-97], 55% [39-70] and 98% [96-99] respectively. Of eleven false-negative samples, RT-PCR Ct-values were higher than all RT-PCR positive test results (27 vs 22, p=0.012). Of twenty false-positive samples, none were culture positive and two tested positive in D-IF. Sensitivity, specificity, PPV and NPV for BNR were 79% [73-85], 98% [96-99], 97% [93-99] and 88% [84-91]. Of the 42 false-negative samples the median Ct-value was higher than that of all RT-PCR positive samples (31 vs 23, p<0.0001). Five false-positive samples were detected. Three of these tested positive for RSV in virus isolation and D-IF. CONCLUSIONS: RADTs have a high specificity with BNR being superior to BNI. However, their relative low sensitivity limits their usefulness for clinical decision making in a tertiary care paediatric hospital.


Subject(s)
Antigens, Viral/analysis , Diagnostic Tests, Routine/methods , Influenza, Human/diagnosis , Respiratory Syncytial Virus Infections/diagnosis , Tertiary Healthcare/methods , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Orthomyxoviridae , Predictive Value of Tests , Sensitivity and Specificity , Time Factors
5.
Clin Microbiol Infect ; 21(10): 964.e1-8, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26100374

ABSTRACT

In 2005 human bocavirus (HBoV) was discovered in respiratory tract samples of children. The role of HBoV as the single causative agent for respiratory tract infections remains unclear. Detection of HBoV in children with respiratory disease is frequently in combination with other viruses or bacteria. We set up an algorithm to study whether HBoV alone can cause severe acute respiratory tract infection (SARI) in children. The algorithm was developed to exclude cases with no other likely cause than HBoV for the need for admission to the paediatric intensive care unit (PICU) with SARI. We searched for other viruses by next-generation sequencing (NGS) in these cases and studied their HBoV viral loads. To benchmark our algorithm, the same was applied to respiratory syncytial virus (RSV)-positive patients. From our total group of 990 patients who tested positive for a respiratory virus by means of RT-PCR, HBoV and RSV were detected in 178 and 366 children admitted to our hospital. Forty-nine HBoV-positive patients and 72 RSV-positive patients were admitted to the PICU. We found seven single HBoV-infected cases with SARI admitted to PICU (7/49, 14%). They had no other detectable virus by NGS. They had much higher HBoV loads than other patients positive for HBoV. We identified 14 RSV-infected SARI patients with a single RSV infection (14/72, 19%). We conclude that our study provides strong support that HBoV can cause SARI in children in the absence of viral and bacterial co-infections.


Subject(s)
Human bocavirus/isolation & purification , Parvoviridae Infections/epidemiology , Parvoviridae Infections/pathology , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/pathology , Child, Preschool , Female , Hospitals , Humans , Infant , Infant, Newborn , Male , Parvoviridae Infections/virology , Real-Time Polymerase Chain Reaction , Respiratory Syncytial Virus Infections/epidemiology , Respiratory Syncytial Virus Infections/pathology , Respiratory Syncytial Virus Infections/virology , Respiratory Syncytial Viruses/isolation & purification , Respiratory Tract Infections/virology , Retrospective Studies , Sequence Analysis, DNA
6.
Pediatr Cardiol ; 36(2): 409-16, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25194576

ABSTRACT

The underlying etiology of dilated cardiomyopathy (DCM) in children varies, 14-22% is secondary to myocarditis, and the majority remains idiopathic. Etiology has prognostic value; however, 'a clinical diagnosis of myocarditis' has been frequently used because the gold standard [endomyocardial biopsy (EMB)] is often not performed. Therefore, a consistent diagnostic approach and interpretation is needed. In this multicenter study, we evaluated the diagnostic approach and interpretation of the viral results in children with myocarditis and idiopathic DCM. We included 150 children with DCM, of whom 103 were assigned the diagnosis myocarditis (n = 21) or idiopathic DCM (n = 82) by the attending physician. Viral tests were performed in 97/103 patients, in only 34% (n = 35) some of the tests were positive. Of those patients, we evaluated the probability of the assigned diagnosis using the viral test results. We classified viral test results as reflecting definite or probable myocarditis in 14 children and possible or unlikely myocarditis in 21 children. Based on this classification, 23% of patients were misclassified. We found that in children with DCM, the diagnostic approach varied and the interpretation was mainly based on viral results. Since a 'clinical diagnosis of myocarditis' has been frequently used in daily practice because of the lack of EMB results, a uniform protocol is needed. We propose to use viral test results in several steps (blood PCR, serology, PCR and/or cultures of the gastro-intestinal and respiratory tract, and EMB results) to estimate the probability of myocarditis.


Subject(s)
Cardiomyopathy, Dilated/diagnosis , Cardiomyopathy, Dilated/etiology , Myocarditis/complications , Biopsy , Endocardium/pathology , Endomyocardial Fibrosis , Humans , Myocarditis/virology , Myocardium/pathology , Polymerase Chain Reaction , Serologic Tests
7.
Neth J Med ; 72(9): 442-8, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25387613

ABSTRACT

Currently, West Africa is facing the largest outbreak of Ebola virus disease (EVD) in history. The virus causing this outbreak, the Zaire Ebolavirus (EBOV), belongs to the genus Ebolavirus which together with the genus Marburgvirus forms the family of the Filoviridae. EBOV is one of the most virulent pathogens among the viral haemorrhagic fevers, and case fatality rates up to 90% have been reported. Mortality is the result of multi-organ failure and severe bleeding complications. By 18 September 2014, the WHO reported of 5335 cases (confirmed, suspected and probable) with 2622 deaths, resulting in a case fatality rate of around 50%. This review aims to provide an overview of EVD for clinicians, with the emphasis on pathogenesis, clinical manifestations, and treatment options.


Subject(s)
Disease Outbreaks , Hemorrhagic Fever, Ebola/therapy , Hemorrhagic Fever, Ebola/transmission , Africa, Western/epidemiology , Hemorrhagic Fever, Ebola/diagnosis , Hemorrhagic Fever, Ebola/epidemiology , Hemorrhagic Fever, Ebola/virology , Humans
8.
Neuromolecular Med ; 10(1): 24-39, 2008.
Article in English | MEDLINE | ID: mdl-18196479

ABSTRACT

Epidemiological studies of the Guamanian variants of amyotrophic lateral sclerosis (ALS) and parkinsonism, amyotrophic lateral sclerosis-parkinsonism dementia complex (ALS-PDC), have shown a positive correlation between consumption of washed cycad seed flour and disease occurrence. Previous in vivo studies by our group have shown that the same seed flour induces ALS and PDC phenotypes in out bred adult male mice. In vitro studies using isolated cycad compounds have also demonstrated that several of these are neurotoxic, specifically, a number of water insoluble phytosterol glucosides of which beta-sitosterol beta-D: -glucoside (BSSG) forms the largest fraction. BSSG is neurotoxic to motor neurons and other neuronal populations in culture. The present study shows that an in vitro hybrid motor neuron (NSC-34) culture treated with BSSG undergoes a dose-dependent cell loss. Surviving cells show increased expression of HSP70, decreased cytosolic heavy neurofilament expression, and have various morphological abnormalities. CD-1 mice fed mouse chow pellets containing BSSG for 15 weeks showed motor deficits and motor neuron loss in the lumbar and thoracic spinal cord, along with decreased glutamate transporter labelling, and increased glial fibrillary acid protein reactivity. Other pathological outcomes included increased caspase-3 labelling in the striatum and decreased tyrosine-hydroxylase labelling in the striatum and substantia nigra. C57BL/6 mice fed BSSG-treated pellets for 10 weeks exhibited progressive loss of motor neurons in the lumbar spinal cord that continued to worsen even after the BSSG exposure ended. These results provide further support implicating sterol glucosides as one potential causal factor in the motor neuron pathology previously associated with cycad consumption and ALS-PDC.


Subject(s)
Amyotrophic Lateral Sclerosis/pathology , Dementia/pathology , Motor Neurons/pathology , Parkinsonian Disorders/pathology , Sitosterols/pharmacology , Amyotrophic Lateral Sclerosis/chemically induced , Amyotrophic Lateral Sclerosis/metabolism , Animals , Caspase 3/metabolism , Cells, Cultured , Corpus Striatum/metabolism , Corpus Striatum/pathology , Dementia/chemically induced , Dementia/metabolism , Diet , HSP70 Heat-Shock Proteins/metabolism , Male , Mice , Motor Neurons/drug effects , Parkinsonian Disorders/chemically induced , Parkinsonian Disorders/metabolism , Spinal Cord/metabolism , Spinal Cord/pathology , Substantia Nigra/metabolism , Substantia Nigra/pathology , Tyrosine 3-Monooxygenase/metabolism
9.
Neuroscience ; 136(2): 381-6, 2005.
Article in English | MEDLINE | ID: mdl-16216425

ABSTRACT

Small molecule neurotransmitters, such as dopamine, have been shown to regulate cell cycles in the developing brain [Spencer GE, Klumperman J, Syed NI (1998) Neurotransmitters and neurodevelopment: Role of dopamine in neurite outgrowth, target selection and specific synapse formation. Perspect Dev Neurobiol 5:451-467; Ohtani N, Goto T, Waeber C, Bhide PG (2003) Dopamine modulates cell cycle in the lateral ganglionic eminence. J Neurosci 23:2840-2850] and may provide an alternative to traditional growth factors for the regulation of neurogenesis. Specifically, the dopamine D3 receptor appears to play an important role in neural development, and shows a persistent expression through adulthood in the proliferative subventricular zone [Diaz J, Ridray S, Mignon V, Griffon N, Schwartz JC, Sokoloff P (1997) Selective expression of dopamine D3 receptor mRNA in proliferative zones during embryonic development of the rat brain. J Neurosci 17:4282-4292]. Furthermore, pharmacological stimulation of D3 receptors promotes proliferation of adult subventricular zone cells, both in vitro [Coronas V, Bantubungi K, Fombonne J, Krantic S, Schiffmann SN, Roger M (2004) Dopamine D3 receptor stimulation promotes the proliferation of cells derived from the post-natal subventricular zone. J Neurochem 91:1292-1301] and in vivo [Van Kampen JM, Hagg T, Robertson HA (2004) Induction of neurogenesis in the adult rat subventricular zone and neostriatum following dopamine D3 receptor stimulation. Eur J Neurosci 19:2377-2387]. In earlier work, we have demonstrated the induction of cell proliferation in the subventricular zone of the adult rat brain accompanied by a dramatic 10-fold induction of neurogenesis in the neighboring neostriatum, following administration of the preferential D3 receptor agonist, 7-hydroxy-N,N-di-n-propyl-2-aminotetralin [Van Kampen JM, Hagg T, Robertson HA (2004) Induction of neurogenesis in the adult rat subventricular zone and neostriatum following dopamine D3 receptor stimulation. Eur J Neurosci 19:2377-2387]. Dopamine D3 receptors have also been found in the substantia nigra [Diaz J, Pilon C, Le Foll B, Gross C, Triller A, Schwartz JC, Sokoloff P (2000) Dopamine D3 receptors expressed by all mesencephalic dopamine neurons. J Neurosci 20:8677-8684], a region of the adult brain shown to exhibit ongoing cytogenesis and neurogenic potential [Lie DC, Dziewczapolski G, Willhoite AR, Kaspar BK, Shults CW, Gage FH (2002) The adult substantia nigra contains progenitor cells with neurogenic potential. J Neurosci 22:6639-6649; Zhao M, Momma S, Delfani K, Carlen M, Cassidy RM, Johansson CB, Brismar H, Shupliakov O, Frisen J, Janson AM (2003) Evidence for neurogenesis in the adult mammalian substantia nigra. Proc Natl Acad Sci U S A 100:7925-7930]. We have found that chronic intraventricular administration of 7-hydroxy-N,N-di-n-propyl-2-aminotetralin triggers a profound induction of cell proliferation in the rat substantia nigra and promotes the adoption of a neuronal phenotype in a proportion of these newly generated cells.


Subject(s)
Dopamine Agonists/pharmacology , Receptors, Dopamine D3/drug effects , Substantia Nigra/growth & development , Animals , Antimetabolites , Bromodeoxyuridine , Cell Proliferation/drug effects , Female , Glial Fibrillary Acidic Protein/metabolism , Injections, Intraventricular , Neuroglia/drug effects , Neurons/drug effects , Proliferating Cell Nuclear Antigen/metabolism , Rats , Rats, Sprague-Dawley , Stimulation, Chemical , Substantia Nigra/cytology , Substantia Nigra/drug effects , Tetrahydronaphthalenes/administration & dosage , Tetrahydronaphthalenes/pharmacology
10.
Neuroscience ; 116(1): 307-14, 2003.
Article in English | MEDLINE | ID: mdl-12535962

ABSTRACT

Levodopa-induced dyskinesias are abnormal involuntary movements that develop as a side-effect of long-term treatment with levodopa for Parkinson's disease. The mechanisms underlying such effects are unclear but may include abnormal stimulation of dopamine D(3) receptors. Elevations in dopamine D(3) receptor mRNA and binding are seen in the denervated striatum of hemiparkinsonian rats treated chronically with levodopa, and these changes correlate well with behavioural sensitization in this model. Further investigation of dopamine D(3) receptor involvement in levodopa-induced dyskinesias is hampered by the lack of appropriately selective ligands for this receptor. Here, in vivo administration of an antisense oligonucleotide designed to reduce striatal dopamine D(3) receptor expression provides a level of specificity not available through traditional pharmacological approaches. Following chronic treatment with levodopa, hemiparkinsonian rats received intrastriatal infusion of oligonucleotide antisense to dopamine D(3) receptor mRNA for 5 days. Antisense treatment effectively and selectively reduced striatal dopamine D(3) receptor binding and blocked behavioural sensitization to the effects of repeated levodopa. These findings confirm the importance of the D3 receptor in the expression of behavioural sensitization to levodopa in animals with dopaminergic denervation and contribute to our limited understanding of the functional significance of this receptor. In that sensitization to the effects of repeated levodopa in this setting may be analogous to medication-induced dyskinesias in humans, our findings furthermore suggest that drugs which block D(3) function may be helpful in the treatment of dyskinesias, without necessarily exacerbating Parkinsonism.


Subject(s)
Corpus Striatum/metabolism , Dopamine Agents , Levodopa , Nucleus Accumbens/metabolism , Oligoribonucleotides, Antisense/pharmacology , Receptors, Dopamine D2/metabolism , Animals , Autoradiography , Behavior, Animal/drug effects , Brain/metabolism , Dopamine Agents/administration & dosage , Dopamine Agents/adverse effects , Levodopa/administration & dosage , Levodopa/adverse effects , Male , Oligoribonucleotides, Antisense/administration & dosage , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Receptors, Dopamine D1/metabolism , Receptors, Dopamine D3
12.
Neuroscience ; 101(3): 629-35, 2000.
Article in English | MEDLINE | ID: mdl-11113312

ABSTRACT

Tardive dyskinesia develops as a common complication of long-term neuroleptic use. The emergence of such dyskinesias may reflect a shift in the balance of dopamine D(1) and D(2) receptor-mediated activity, with a relative increase in activity in the D(1) receptor-regulated direct striatonigral pathway. In rats, chronic treatment with the antipsychotic fluphenazine triggers a syndrome of vacuous chewing movements, which are attenuated by dopamine D(1) receptor antagonists. A similar syndrome can be seen in drug-naive animals following acute administration of selective dopamine D(1) receptor agonists. However, not all dopamine D(1) receptor agonists elicit these mouth movements. Thus, some investigators have suggested the existence of novel subtypes of the dopamine D(1) receptor. In these studies, we sought to clarify the role of the dopamine D(1A) receptor in vacuous chewing movements induced both by the selective dopamine D(1) receptor agonist SKF 38393, as well as by chronic neuroleptic administration, using in vivo oligonucleotide antisense to dopamine D(1A) receptor messenger RNA. Intrastriatal antisense treatment significantly and selectively attenuated striatal dopamine D(1) receptor binding, accompanied by reductions in SKF 38393- and chronic fluphenazine-induced vacuous chewing movements. These findings suggest that the dopamine D(1A) receptor plays an important role in the expression of vacuous chewing movements in a rodent model of tardive dyskinesia and may contribute to the pathogenesis of the human disorder. This may have important implications for the treatment of tardive dyskinesia in humans.


Subject(s)
Dyskinesia, Drug-Induced/metabolism , Neostriatum/drug effects , Neurons/drug effects , Receptors, Dopamine D1/drug effects , Receptors, Dopamine D1/metabolism , 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine/pharmacology , Animals , Antipsychotic Agents/adverse effects , Behavior, Animal/drug effects , Behavior, Animal/physiology , Binding Sites/drug effects , Binding Sites/physiology , Disease Models, Animal , Dopamine Agonists/pharmacology , Dyskinesia, Drug-Induced/pathology , Dyskinesia, Drug-Induced/physiopathology , Fluphenazine/pharmacology , Male , Mastication/drug effects , Mastication/physiology , Neostriatum/pathology , Neostriatum/physiopathology , Neurons/metabolism , Neurons/pathology , RNA, Messenger/drug effects , RNA, Messenger/metabolism , Raclopride/pharmacology , Rats , Rats, Sprague-Dawley , Receptors, Dopamine D1/genetics , Receptors, Dopamine D2/drug effects , Receptors, Dopamine D2/metabolism , Tritium
13.
Synapse ; 37(3): 171-8, 2000 Sep 01.
Article in English | MEDLINE | ID: mdl-10881039

ABSTRACT

The plasma membrane dopamine transporter is located on presynaptic nerve terminals and is responsible for the termination of dopaminergic neurotransmission via dopamine reuptake. The dopamine transporter may also contribute to the pathogenesis of Parkinson disease. Dopamine transporter expression correlates well with susceptibility to neuronal degeneration in 1-methyl-4-phenyl-1,2,3,6 -tetrahydropyridine (MPTP)-induced parkinsonism. Recent studies have implicated the dopamine transporter in the uptake of both this neurotoxin and its metabolite, MPP(+), as well as another experimental neurotoxin, 6-hydroxydopamine. In these studies we examined the role of the dopamine transporter in the neurotoxicity of both MPP(+) and 6-hydroxydopamine in the rat brain using in vivo administration of phosphorothioate antisense oligonucleotides targeting dopamine transporter mRNA. Infusion of dopamine transporter antisense (1 nmol/day, 7 days) into the left substantia nigra pars compacta resulted in reduced (3)H-WIN 35-428 binding in the left striatum and significant levodopa and amphetamine-induced contralateral rotations. Unilateral pretreatment with dopamine transporter antisense prior to bilateral intrastriatal infusion of either MPP(+) or 6-hydroxydopamine resulted in asymmetrical striatal (3)H-WIN 35-428 binding and dopamine content as well as significant apomorphine-induced ipsilateral rotations, suggesting neuroprotection of nigrostriatal neurons on the antisense-treated side. Thus, the dopamine transporter appears to play a critical role in determining susceptibility to the experimental neurotoxins MPP(+) and 6-hydroxydopamine. In light of this, the dopamine transporter may prove useful, both as a marker for susceptibility to Parkinson's disease and as a target for therapeutic intervention.


Subject(s)
1-Methyl-4-phenylpyridinium/toxicity , Carrier Proteins/genetics , Cytoprotection/physiology , Membrane Glycoproteins , Membrane Transport Proteins , Nerve Tissue Proteins , Oligonucleotides, Antisense/pharmacology , Oxidopamine/toxicity , RNA, Messenger/antagonists & inhibitors , Substantia Nigra/drug effects , Amphetamine/pharmacology , Animals , Apomorphine/pharmacology , Autoradiography , Carrier Proteins/metabolism , Cocaine/analogs & derivatives , Cocaine/metabolism , Corpus Striatum/drug effects , Corpus Striatum/metabolism , Dopamine Plasma Membrane Transport Proteins , Levodopa/pharmacology , Male , Microinjections , Motor Activity/drug effects , Rats , Rats, Sprague-Dawley , Substantia Nigra/metabolism , Tritium
14.
Neuroscience ; 98(1): 61-7, 2000.
Article in English | MEDLINE | ID: mdl-10858612

ABSTRACT

Dyskinesias are abnormal involuntary movements which develop as a side-effect of long-term treatment with levodopa in patients with Parkinson's disease. The pathophysiology underlying these dyskinesias remains unclear, although, it has been suggested that heightened activity of dopamine D(1) receptor-bearing striatonigral neurons may play a key role. Chronic pulsatile levodopa administration to hemiparkinsonian rats results in sensitization of rotational responses to apomorphine. This sensitization is thought to be analogous to levodopa-induced dyskinesias in humans. In these studies, we further clarify the role of the dopamine D(1A) receptor in this rodent model of levodopa-induced dyskinesias using an in vivo oligonucleotide antisense approach. Hemiparkinsonian rats received twice daily injections of levodopa for three weeks followed by intrastriatal infusion of dopamine D(1A) receptor antisense (7nmol/day, three days), a scrambled missense control sequence, or saline. Those animals treated with antisense displayed significantly fewer apomorphine-induced rotations than saline- or missense-treated controls.By reducing dopamine D(1A) receptor expression, we were able to attenuate sensitization of the response to apomorphine resulting from chronic pulsatile levodopa treatment. Thus, the dopamine D(1A) receptor appears to play a significant role in levodopa-induced dyskinesias and warrants further examination. These findings may have important implications for the development of selective treatment strategies designed to alleviate parkinsonian symptoms, while minimizing motor complications.


Subject(s)
Antiparkinson Agents/adverse effects , Dyskinesia, Drug-Induced/physiopathology , Levodopa/adverse effects , Oligonucleotides, Antisense/pharmacology , Receptors, Dopamine D1/genetics , Animals , Apomorphine/pharmacology , Autoradiography , Behavior, Animal/drug effects , Behavior, Animal/physiology , Cocaine/analogs & derivatives , Cocaine/metabolism , Cocaine/pharmacology , Denervation , Disease Models, Animal , Dopamine Antagonists/metabolism , Dopamine Antagonists/pharmacology , Dopamine Uptake Inhibitors/metabolism , Dopamine Uptake Inhibitors/pharmacology , Dyskinesia, Drug-Induced/genetics , Gene Expression/physiology , Male , Oxidopamine , Phenotype , RNA, Messenger/metabolism , Raclopride/metabolism , Raclopride/pharmacology , Rats , Rats, Sprague-Dawley , Receptors, Dopamine D1/analysis , Receptors, Dopamine D1/metabolism , Receptors, Dopamine D2/analysis , Receptors, Dopamine D2/metabolism , Rotation , Substantia Nigra/chemistry , Substantia Nigra/physiopathology , Sympatholytics , Tritium
15.
Neuropharmacology ; 36(11-12): 1679-88, 1997.
Article in English | MEDLINE | ID: mdl-9517439

ABSTRACT

The neuropeptide cholecystokinin (CCK) has been shown to interact with dopamine in various ways, including attenuation of dopamine D1 receptor-mediated vacuous chewing and grooming. While we have demonstrated a clear role for the CCK(A) receptor in the attenuation of dopamine D1 agonist-induced vacuous chewing, studies of grooming yielded anomalous results. We examined the effects of selective CCK receptor antagonists on the attenuation of SKF 38393-induced grooming by the CCKB agonist CCK-4. Administration of SKF 38393 (5 mg/kg s.c.) to male Sprague-Dawley rats resulted in a significant increase in grooming which was reduced to control levels by CCK-4 (20 mg/kg i.p.). Pretreatment with either the CCKA receptor antagonist devazepide or the CCK(B) receptor antagonist L-365,260 significantly attenuated this effect over a range of doses (20, 100, 500 microg/kg i.p.). The suppression of dopamine D1 agonist-induced grooming by CCK-4 does not appear to reflect a non-specific effect of anxiogenesis, as it was unaffected by the anxiolytic diazepam. The CCK receptor antagonists alone were without behavioural effect. Taken together with previous studies in models of anxiety and analgesia, our findings lend further support to the hypothesis that CCK-4 may act at a novel receptor subtype.


Subject(s)
Cholecystokinin/pharmacology , Dopamine Agonists/pharmacology , Grooming/drug effects , Phenylurea Compounds , Receptors, Cholecystokinin/antagonists & inhibitors , Receptors, Dopamine D1/agonists , 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine/pharmacology , Animals , Behavior, Animal/drug effects , Benzodiazepinones/pharmacology , Devazepide , Diazepam/pharmacology , GABA Modulators/pharmacology , Hormone Antagonists/pharmacology , Male , Rats , Rats, Sprague-Dawley
16.
Eur J Pharmacol ; 298(1): 7-15, 1996 Feb 29.
Article in English | MEDLINE | ID: mdl-8867913

ABSTRACT

The effects of cholecystokinin (CCK) on behavioural responses to the dopamine D1 receptor agonist (+/- )SKF 38393 ((+/- )-2,3,4,5-tetrahydro-7,8- dihydroxy-1-phenyl-1H-3-benzazepine HCl) were studied in the rat. SKF 38393 (5 mg/kg s.c.) induced stereotyped grooming and vacuous chewing movements. Both responses were inhibited by CCK-8S (10-50 micrograms/kg i.p.), but the preferential CCKB receptor agonist CCK-4 (20-100 micrograms/kg i.p.) attenuated SKF 38393-induced grooming only. Suppression of SKF 38393-induced grooming and vacuous chewing movements by CCK-8S was blocked by the selective CCKA receptor antagonist MK-329 (also known as devazepide or L-364,718) (0.1, 0.3 mg/kg i.p.) but unaffected by the CCKB receptor antagonist L-365,260 (0.1, 0.3 mg/kg i.p.). We conclude that CCK can modify dopamine-mediated behavioural responses, possibly reflecting an action post-synaptic to dopamine terminals. The effect on dopamine D1 receptor agonist-induced vacuous chewing movements is probably mediated by CCKA receptors, while the effect on grooming may reflect an interaction with the CCKA receptor and/or a novel CCKB receptor subtype.


Subject(s)
Behavior, Animal/drug effects , Cholecystokinin/pharmacology , Receptors, Dopamine D1/drug effects , 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine/pharmacology , Animals , Benzodiazepinones/pharmacology , Devazepide , Grooming/drug effects , Male , Rats , Rats, Sprague-Dawley
17.
J Rheumatol ; 22(8): 1520-6, 1995 Aug.
Article in English | MEDLINE | ID: mdl-7473477

ABSTRACT

OBJECTIVE: To study the effect of interleukin-1 (IL-1) on the synthesis of proteoglycans biglycan (DSPG-I) and decorin (DSPG-II) in intact bovine articular cartilage. METHODS: Cartilage bearing sesamoid bones from the metacarpophalangeal joint were cultured with 10 ng/ml IL-1 for 2 days and labelled with [35S] sulfate. One sesamoid bone from each animal had been labelled ex vivo. The remaining 2 were cultured with IL-1 and allowed to recover in control medium before labelling. Control cultures were maintained in medium without IL-1 and labelled concurrently with the experimental series. The dermatan sulfate proteoglycans were purified from 4 M guanidinium chloride extracts of the cartilage by gel filtration on Sepharose CL-2B and CL-4B, on which they appeared as a single peak. Biglycan and decorin were separated by sodium dodecyl sulfide polyacrylamide gel electrophoresis in high salt. Individual lanes from the gel were cut in slices, which were dissolved and counted for radioactivity. RESULTS: Ex vivo, biglycan accounted for 4% and decorin for 2% of total incorporated sulfate. IL-1 reduced the synthesis of biglycan to 77% of the level of cultured controls and that of decorin to 73%. The synthesis of both proteoglycans returned to the control levels when the IL-1 was removed. IL-1 (10 ng/ml, 2 days) had no significant effect on total proteoglycan synthesis. CONCLUSION: The inhibition of synthesis of biglycan and decorin by IL-1 might be important in the pathophysiology of cartilage destruction in rheumatic diseases.


Subject(s)
Cartilage, Articular/metabolism , Interleukin-1/pharmacology , Proteoglycans/biosynthesis , Animals , Biglycan , Cattle , Chromatography, Agarose , Decorin , Electrophoresis, Polyacrylamide Gel , Extracellular Matrix Proteins , Organ Culture Techniques , Sesamoid Bones , Time Factors
18.
J Endocrinol ; 146(1): 87-94, 1995 Jul.
Article in English | MEDLINE | ID: mdl-7561625

ABSTRACT

The pituitary-ovarian axis was studied after withdrawal of thyroid hormone in 131I-radiothyroidectomized adult female rats. Oestrous cycles became prolonged and irregular within 2 weeks after the supply of thyroid hormone was stopped. If an LH surge occurred in hypothyroid rats on the day of vaginal pro-oestrus it was significantly greater in rats which had been made hypothyroid for 4-5 weeks than in controls; in hypothyroid rats with an LH surge on pro-oestrus, plasma progesterone showed a rise similar to that in controls at pro-oestrus; the ovulation rate was decreased in hypothyroid rats. About half of the rats from which blood was sampled daily in the afternoon between 7 and 18 days after tri-iodothyronine (T3) withdrawal had 1 day of pro-oestrus; on this day the LH surge was higher than in controls. On days 2 and 1 before and days 1 and 2 after this pro-oestrus, plasma progesterone was similar to that of controls on days 2 and 1 before and days 1 and 2 after pro-oestrus respectively. However, progesterone was higher in the period before and after these days. The other hypothyroid rats showed no pro-oestrus and no LH surge during this period, while their plasma progesterone levels were high on all days. On the morning of day 10 after T3 withdrawal and 5 days after the preceding pro-oestrus, most hypothyroid rats had high progesterone and low oestradiol plasma levels.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Hypothyroidism/physiopathology , Ovary/physiopathology , Pituitary Gland/physiopathology , Proestrus , Animals , Estradiol/blood , Female , Gonadotropin-Releasing Hormone/pharmacology , Hypothyroidism/blood , Luteinizing Hormone/blood , Ovulation/drug effects , Progesterone/blood , Rats , Rats, Wistar , Time Factors
19.
J Psychol ; 127(2): 233-43, 1993 Mar.
Article in English | MEDLINE | ID: mdl-8336298

ABSTRACT

These two studies pursued the notion that there are individual differences of considerable generality in the extent to which individuals estimate the size of objects, including body image and physical objects such as a blank card. In the first study, 79 female undergraduate students estimated the width of their own bodies (head, shoulders, waist, and hips), the waist of a standard "real" person, the bodies of two life-size wooden figures, and three boxes. In the second study, 60 female undergraduate students estimated the width of their bodies, three boxes, and two blank cards. Errors in estimation, computed as the difference between estimate and true value divided by the true value, were obtained from all subjects. Correlations between body-image errors and all other errors in estimation were positive in both studies, except for one correlation of - .02. Factor analyses of the correlations between the error scores in each study indicated a substantial general factor, although some residual common variance remained. Results supported the proposition that individuals differ in a consistent fashion across a wide range of size-estimation situations.


Subject(s)
Body Image , Generalization, Psychological , Individuality , Size Perception , Adult , Body Constitution , Discrimination Learning , Female , Humans
20.
J Affect Disord ; 11(3): 275-80, 1986.
Article in English | MEDLINE | ID: mdl-2951414

ABSTRACT

The effectiveness of lithium prophylaxis in bipolar affective disorders is generally supported in the literature. The effects in this group, as well as in unipolar depressions and schizo-affective disorders were studied, using an individual retrospective control method, and the Life Table method. Lithium prophylaxis resulted in a substantial decrease in the number of episodes and hospital admissions in bipolar and schizo-affective disorders. In addition, these two groups showed frequent relapses after termination of the prophylaxis. The number of episodes preceding the prophylaxis and the absence of unipolar depression are found to be predictors of effectiveness. The consequences of patient selection and of inconclusive diagnostic criteria are pointed out.


Subject(s)
Bipolar Disorder/prevention & control , Depressive Disorder/prevention & control , Lithium/therapeutic use , Psychotic Disorders/prevention & control , Adult , Bipolar Disorder/psychology , Depressive Disorder/psychology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Psychotic Disorders/psychology
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