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1.
Tijdschr Psychiatr ; 65(8): 479-483, 2023.
Artículo en Neerlandesa | MEDLINE | ID: mdl-37755927

RESUMEN

BACKGROUND: Several European countries are reforming their mental healthcare program. This implies an increase of pressure on outpatient care and also in Flanders are waiting times long in the outpatient care and patients don’t receive timely care. Hitherto, a nursing consultation in mental health care is a fairly new concept of care. AIM: To explore mental health care professionals’ point of view on outpatient nursing consultation in mental health care. METHOD: An explorative qualitative research with semi-structured interviews was conducted. Fifteen mental health care professionals from different wards were interviewed. A thematic analysis was used. RESULTS: Three main topics emerged: content, purpose and conditions for nursing consultation. The central topic of consultation should be patients’ quality of life when dealing with a mental illness and how support can be offered. The respondents found that the nurse functions as a mediator and provides continuity by playing an important role in observing and reporting. CONCLUSION: The research contributes to identifying the mental healthcare professionals’ view on nursing consultation in outpatient mental health care. The implementation of nursing consultation has to meet several conditions such as the nurse’s competences and training, interprofessional collaboration and organizational concerns e.g. financing and staffing.


Asunto(s)
Pacientes Ambulatorios , Calidad de Vida , Humanos , Recursos Humanos , Atención Ambulatoria , Derivación y Consulta
2.
Tijdschr Psychiatr ; 65(1): 46-49, 2023.
Artículo en Neerlandesa | MEDLINE | ID: mdl-36734690

RESUMEN

Autism spectrum disorder and psychotic disorders/schizophrenia are separate disorders in the DSM-5. Due to overlapping symptoms and increased frequency in comorbidity they can be a diagnostic and therapeutic challenge in clinical practice. Relevant literature regarding the correlation between these disorders is discussed and linked to a case-report. An increased prevalence of autism/autistic traits is observed within psychotic patients and vice versa. Common symptoms and risk-factors, but also differential factors, are described. Despite of several hypotheses concerning increased frequency in comorbidity, no clear explanation was found so far. Little is known concerning treatment in case of comorbidity. In this case-report there was significant amelioration after treatment with an atypical antipsychotic. Psycho-education and attention to structuring are also important elements of the treatment plan.


Asunto(s)
Trastorno del Espectro Autista , Trastornos Psicóticos , Esquizofrenia , Humanos , Trastorno del Espectro Autista/diagnóstico , Trastorno del Espectro Autista/epidemiología , Trastorno del Espectro Autista/terapia , Comorbilidad , Diagnóstico Diferencial , Trastornos Psicóticos/diagnóstico , Esquizofrenia/diagnóstico , Esquizofrenia/epidemiología , Adolescente
3.
Tijdschr Psychiatr ; 64(7): 466-469, 2022.
Artículo en Neerlandesa | MEDLINE | ID: mdl-36040092

RESUMEN

Both Cushing’s and pseudo-Cushing’s syndrome involve a state of hypercortisolism. Cushing’s syndrome is a progressive multisystemic disease, caused by either the administration of corticosteroids, or the overproduction of cortisol by a tumoral process. In pseudo-Cushing’s syndrome the HPA-axis is hyperactive due to a pathophysiological process, most frequently caused by depression. The existence of a cyclic variant of Cushing’s syndrome, characterised by intermittent hypercortisolism, complicates the diagnosis in a patient with for example depression. In case of remaining intermittent hypercortisolism after remission of the depression, extreme hypercortisolism and (suspicion of) a tumor, we have to consider a cyclic Cushing syndrome. Also, in patients with treatment resistant depression or depression with atypical features combined with intermittent hypercortisolism psychiatrists have to consider a cyclic Cushing syndrome.


Asunto(s)
Síndrome de Cushing , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/etiología , Depresión/diagnóstico , Diagnóstico Diferencial , Humanos , Hidrocortisona
4.
Tijdschr Psychiatr ; 63(4): 301-304, 2021.
Artículo en Neerlandesa | MEDLINE | ID: mdl-33913147

RESUMEN

Catatonia is a psychomotor syndrome characterised by multiple symptoms like stereotypies - repetitive, abnormally frequent, non-goal-directed movements. A problem is the lack of unanimity regarding the number of symptoms needed for diagnosis. We describe repetitive inappropriate sexual behaviour in a patient with bipolar depression and excited catatonia with Bush-Francis Catatonia Rating Scale score of 12. Electroconvulsive therapy resulted in disappearance of catatonia and inappropriate sexual behaviour and remission of depression. A recurrent episode with similar inappropriate sexual behaviour was successfully treated with electroconvulsive therapy. We interpreted the repetitive inappropriate sexual behaviour as a catatonic stereotypy. Similar stereotypies are reported in children with autism. Tics and self-injury in patients with autism are described as a stereotypy within catatonia. The agitated depression is another possible diagnosis with the repetitive inappropriate sexual behaviour as an example of psychomotor agitation. More research is needed towards repetitive inappropriate sexual behaviour as a possible stereotypy within catatonia.


Asunto(s)
Catatonia/terapia , Depresión/terapia , Terapia Electroconvulsiva , Agitación Psicomotora/terapia , Conducta Sexual , Catatonia/diagnóstico , Depresión/diagnóstico , Humanos
5.
Tijdschr Psychiatr ; 59(10): 650-654, 2017.
Artículo en Neerlandesa | MEDLINE | ID: mdl-29077142

RESUMEN

BACKGROUND: Neurostimulation is a potentially interesting treatment option for children and adolescents with psychiatric disorders.
AIM: To review the efficacy of two non-invasive neurostimulation techniques, namely repetitive transcranial magnetic stimulation (rtms) and transcranial direct current stimulation (tdcs), in the treatment of child and adolescent psychiatric disorders.
METHOD: We searched the literature research using PubMed.
RESULTS: There is some evidence that rtms is being used to treat unipolar depression, psychosis, autism spectrum disorder, attention deficit hyperactivity disorder and tic disorder. So far, however, very little research has been done on tdcs.
CONCLUSION: Further research is vitally important in order to ensure the safety and efficacy of rtms and tdcs.


Asunto(s)
Psiquiatría del Adolescente , Psiquiatría Infantil , Estimulación Transcraneal de Corriente Directa/métodos , Estimulación Magnética Transcraneal/métodos , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/terapia , Trastorno del Espectro Autista/terapia , Niño , Trastorno Depresivo/terapia , Humanos
6.
Tijdschr Psychiatr ; 59(6): 360-365, 2017.
Artículo en Neerlandesa | MEDLINE | ID: mdl-28613368

RESUMEN

BACKGROUND: Because psychostimulant intoxication can lead to serious health risks for the patient, it is often necessary to ensure that the patient receives both adequate medical surveillance and rapid tranquillisation.
AIM: To find out whether there is scientific evidence that psychopharmacological intervention helps patients with psychostimulant intoxication to manage aggression and agitation.
METHOD: We searched the literature systematically.
RESULTS: Our study showed that intravenous droperidol worked faster and was more effective than intravenous lorazepam in inducing sedation in patients intoxicated with psychostimulants. In other studies the number of patients intoxicated with psychostimulants was too small or the patient population was not described in sufficient detail for any meaningful conclusions to be drawn.
CONCLUSION: So far, research has been so limited that it has not yet provided convincing evidence about the best medication to use in the treatment of aggressive patients intoxicated with psychostimulants.


Asunto(s)
Antipsicóticos/uso terapéutico , Agitación Psicomotora/tratamiento farmacológico , Trastornos Psicóticos/tratamiento farmacológico , Agresión/efectos de los fármacos , Droperidol/uso terapéutico , Humanos
8.
Neurology ; 50(2 Suppl 1): S23-6, 1998 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-9484419

RESUMEN

There is controversy regarding the relationship of structural or biochemical brainstem lesions to "idiopathic" narcolepsy. Most cases of the narcoleptic syndrome are considered to be idiopathic because no structural lesion is detectable, although some cases of secondary narcolepsy are known to be associated with no structural brainstem lesions. Using proton spectroscopy, we determined levels of ventral pontine metabolite pools in 12 normal subjects and 12 subjects with idiopathic narcolepsy. REM sleep is generated in ventral pontine areas. Proton spectroscopy was used to study levels of N-acetyl aspartate (NAA) as a marker of cell mass, creatine and phosphocreatine (Cr + PCr), and choline (Cho). The intensity of the peaks, as determined by the area under the peak (AUP), was measured. The AUP correlates with the quantity of chemical present. In this study, the ratios of NAA to Cr + PCr were similar in normal subjects and in narcoleptic subjects with idiopathic narcolepsy. No differences in measured metabolic ratio were observed in subjects who slept during the scan procedure compared with those who remained awake. Subjects with "symptomatic" narcolepsy accompanied by an obvious structural brain lesion were not studied. Proton spectroscopy of the brain initiates a new kind of neurochemistry, allowing the noninvasive study of metabolic pools in the living human brain without the use of any kind of tracer or radioactive molecule. In this study, there was no evidence of cell loss in the ventral pontine areas of subjects with the narcoleptic syndrome.


Asunto(s)
Encefalopatías/metabolismo , Espectroscopía de Resonancia Magnética , Narcolepsia/etiología , Puente/metabolismo , Adolescente , Adulto , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Encefalopatías/complicaciones , Encefalopatías/diagnóstico , Creatina/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fosfocreatina/metabolismo , Puente/patología , Factores Sexuales
9.
Neurology ; 49(2): 438-44, 1997 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-9270574

RESUMEN

We have carried out single-voxel proton magnetic resonance spectroscopy centered on the putamen both ipsilateral and contralateral to the worst affected side in nine subjects with drug naive idiopathic Parkinson's disease (IPD); seven chronically levodopa-treated dyskinetic IPD subjects; and 11 age-matched healthy controls. Measurements of N-acetylaspartate (NAA)/choline (Cho), NAA/(Creatine + Phosphocreatine) (Cr + PCr), and Cho/(Cr + PCr) were made. We found a significant reduction in NAA/Cho ratios from the putamen contralateral to the most affected side in the drugnaive group (p = 0.009), but not the levodopa-treated IPD groups compared with controls. There were no significant differences in NAA/(Cr + PCr) or Cho/(Cr + PCr) ratios. In untreated IPD, reduced putaminal NAA/Cho ratios may reflect loss of nigrostriatal dopamine terminals or alternatively indicate a functional abnormality of striatal putaminal neurons, such as membrane dysfunction due to striatal deafferentation. This study suggests that NAA/Cho ratios may be affected by L-dopa therapy and this may provide a reversible marker of neuronal dysfunction in the striatum.


Asunto(s)
Antiparkinsonianos/uso terapéutico , Ácido Aspártico/análogos & derivados , Colina/metabolismo , Dopaminérgicos/uso terapéutico , Levodopa/uso terapéutico , Espectroscopía de Resonancia Magnética , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Putamen/metabolismo , Adulto , Anciano , Ácido Aspártico/metabolismo , Creatina/metabolismo , Humanos , Persona de Mediana Edad , Enfermedad de Parkinson/diagnóstico , Fosfocreatina/metabolismo , Protones , Valores de Referencia
10.
Neuropharmacology ; 42(5): 706-13, 2002 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-11985829

RESUMEN

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by selective motor neuron death. The exact mechanism responsible for this selectivity is not clear, although it is known that motor neurons are very sensitive to excitotoxicity. This high sensitivity is due to a high density of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors on their surface and to a limited Ca(2+) buffering capacity. Ca(2+) can enter the cell upon stimulation through voltage-operated Ca(2+) channels and through the Ca(2+)-permeable portion of AMPA receptors. How this Ca(2+) kills motor neurons is incompletely understood. In the present study, we report that kainate (KA)-induced motor neuron death is purely mediated through Ca(2+) entering motor neurons through Ca(2+)-permeable AMPA receptors and that voltage-operated Ca(2+) channels play no significant role. In contrast to what has been observed in other neuronal models or after N-methyl-D-aspartate stimulation, NO synthase inhibition and a number of antioxidants did not protect motor neurons from KA-induced death. Only PD150606, derived from alpha-mercaptoacrylic acid and considered as a selective calpain antagonist, inhibited dose-dependently the KA-induced motor neuron death. However, other calmodulin and calpain inhibitors were not effective. At least part of the inhibitory effect of PD150606 is due to an irreversible inhibition of the Ca(2+) influx through the Ca(2+)-permeable AMPA receptor. These results demonstrate the interesting property of PD150606 to interfere with excitotoxicity-dependent motor neuron death and show that PD150606 is not an exclusive calpain/calmodulin antagonist.


Asunto(s)
Acrilatos/farmacología , Calcio/metabolismo , Calpaína/metabolismo , Ácido Kaínico/antagonistas & inhibidores , Neuronas Motoras/efectos de los fármacos , Inhibición Neural/efectos de los fármacos , Animales , Calcio/antagonistas & inhibidores , Calmodulina/antagonistas & inhibidores , Calmodulina/metabolismo , Calpaína/antagonistas & inhibidores , Muerte Celular/efectos de los fármacos , Muerte Celular/fisiología , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Células Cultivadas , Relación Dosis-Respuesta a Droga , Embrión de Mamíferos , Inhibidores Enzimáticos/farmacología , Agonistas de Aminoácidos Excitadores/farmacología , Ácido Kaínico/farmacología , Neuronas Motoras/citología , Neuronas Motoras/fisiología , Inhibición Neural/fisiología , Ratas , Receptores AMPA/antagonistas & inhibidores , Receptores AMPA/metabolismo
11.
Thromb Haemost ; 79(6): 1171-6, 1998 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-9657444

RESUMEN

To investigate a potential physiological role of the plasminogen/plasmin system in activation of the matrix metalloproteinase (MMP) system, the distribution of latent and active MMP-2 (gelatinase A) or MMP-9 (gelatinase B) was monitored in aorta extracts and in serum-free conditioned cell culture medium obtained from wild-type (WT) mice and from mice with deficiency of tissue-type plasminogen activator (t-PA(-/-)), urokinase-type plasminogen activator (u-PA(-/-)), plasminogen activator inhibitor-1 (PAI-1(-/-)) or plasminogen (Plg(-/-)). In aorta extracts, the contribution of active MMP-2 to the total MMP-2 level ranged between 7 and 16% for the different genotypes, whereas active MMP-9 was not detected. The contribution of active 58 kDa MMP-2 to the total MMP-2 level (active plus latent) ranged between 14 and 29% (mean of 3 experiments) for fibroblasts of the different genotypes, and between 18 and 32% for smooth muscle cells, and was relatively constant in time (7-72 h). The contribution of active 83 kDa MMP-9 to the total MMP-9 level ranged between 15 and 29% for fibroblasts of the different genotypes and was relatively constant in time (24-72 h); corresponding values were 17 to 57% for smooth muscle cells, with the exception of Plg(-/-) smooth muscle cells which had undetectable levels of active MMP-9. Addition of plasmin(ogen) to the cell culture medium of fibroblasts did not significantly affect the distribution of active and latent MMP-2, but resulted in an approximately two-fold enhancement of the contribution of active MMP-9. In macrophages of Plg(-/-) mice, active MMP-9 was detected only when the cells were cultured in the presence of plasminogen. These data indicate that activation of proMMP-2 occurs independently of the physiological plasminogen activators and of plasmin(ogen) in all the cell types evaluated. Activation of proMMP-9 was enhanced in the presence of plasmin(ogen), but active MMP-9 was also detected in fibroblasts of Plg(-/-) mice, indicating that in vivo activation may occur via plasmin(ogen)-independent mechanisms.


Asunto(s)
Colagenasas/metabolismo , Fibrinolisina/fisiología , Gelatinasas/metabolismo , Metaloendopeptidasas/metabolismo , Plasminógeno/fisiología , Animales , Aorta/citología , Células Cultivadas , Medios de Cultivo Condicionados , Medio de Cultivo Libre de Suero , Embrión de Mamíferos/citología , Activación Enzimática , Inducción Enzimática , Femenino , Fibrinolisina/antagonistas & inhibidores , Fibroblastos/enzimología , Marcación de Gen , Macrófagos Peritoneales/enzimología , Masculino , Metaloproteinasa 2 de la Matriz , Metaloproteinasa 9 de la Matriz , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Músculo Liso Vascular/enzimología , Plasminógeno/deficiencia , Plasminógeno/genética , Plasminógeno/farmacología , Inhibidor 1 de Activador Plasminogénico/deficiencia , Inhibidor 1 de Activador Plasminogénico/genética , Piel/citología , Activador de Tejido Plasminógeno/deficiencia , Activador de Plasminógeno de Tipo Uroquinasa/deficiencia , Activador de Plasminógeno de Tipo Uroquinasa/genética
12.
Thromb Haemost ; 82(3): 1127-31, 1999 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-10494776

RESUMEN

Stromelysin-1 (MMP-3) cleaves a 55 kDa kringle 1-4 fragment, containing the lysine-binding site(s) involved in cellular binding, from 92 kDa plasminogen and removes a 17 kDa NH2-terminal fragment, containing the cellular receptor-binding site, from 45 kDa urokinase (u-PA), but a potential role of MMP-3 in the regulation of cellular fibrinolytic activity by affecting binding and/or activation of plasminogen and/or single-chain u-PA has not been established. Human plasminogen (input concentration 100 nM for 4x10(6) cells per ml) was shown to bind specifically to human monocytoid THP-1 cells, to murine MMP-3 deficient smooth muscle cells (SMC) and fibroblasts (1.9, 0.92 and 1.0x10(6) molecules per cell, respectively). Treatment with MMP-3 (final concentration 0-50 nM) of cells saturated with bound plasminogen (about 25 nM), overnight at 37 degrees C, resulted in a dose-dependent reduction of the amount of u-PA activatable plasminogen (reduction to 25-40% of the value in the absence of MMP-3). Immunoblotting with specific monoclonal antibodies and autoradiography of eluates of the cells treated with MMP-3 revealed cleavage of plasminogen into the 55 kDa fragment and miniplasminogen (kringle 5 plus the proteinase domain). Binding of human single chain u-PA (scu-PA) to human THP-1 and HT 1080 cells amounted to 2.5x10(6) and 7.1x10(6) molecules per cell, respectively. Treatment with MMP-3 (final concentration 0-25 nM) of cell-bound u-PA (about 17 nM for THP-1 and 47 nM for HT1080 cells), overnight at 37 degrees C, did not alter cell-associated u-PA activity, measured in a direct chromogenic substrate assay or in a plasminogen-coupled chromogenic substrate assay (residual u-PA activity always > or =85% of that without MMP-3 treatment). Autoradiography of 125I-labeled u-PA moieties, removed from the cells by treatment with acid or with phosphatidylinositol phospholipase C, confirmed that u-PA remained essentially intact after MMP-3 treatment. These data indicate that MMP-3 may downregulate cell-associated plasmin activity by decreasing the amount of activatible plasminogen, without affecting cell-bound u-PA activity.


Asunto(s)
Metaloproteinasa 3 de la Matriz/metabolismo , Plasminógeno/metabolismo , Sitios de Unión , Línea Celular , Membrana Celular/metabolismo , Compuestos Cromogénicos , Fibrinolisina/metabolismo , Fibrinólisis/fisiología , Humanos , Radioisótopos de Yodo , Cinética , Plasminógeno/química , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Activador de Plasminógeno de Tipo Uroquinasa/química , Activador de Plasminógeno de Tipo Uroquinasa/metabolismo
13.
Thromb Haemost ; 68(2): 170-9, 1992 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-1412163

RESUMEN

A recombinant chimeric plasminogen activator consisting of a humanized monoclonal antibody specific for cross-linked human fibrin (MA-15C5Hu) and a 32 kDa single-chain urokinase-type plasminogen activator (scu-PA-32k) comprising amino acids Leu144-Leu411, MA-15C5Hu/scu-PA-32k, was previously found to have a 12-fold higher fibrinolytic potency than recombinant scu-PA-32k towards a human plasma clot in a human plasma milieu in vitro (Vandamme et al., Eur J Biochem 1992; 205: 139-46). Therefore, the thrombolytic and pharmacokinetic properties of MA-15C5Hu/scu-PA-32k were compared with those of recombinant single-chain urokinase-type plasminogen activator (scu-PA) in 3 different venous thrombosis models in vivo. In hamsters with a pulmonary embolus consisting of a human plasma clot, the thrombolytic potency (% lysis per dose in mg/kg administered) of MA-15C5Hu/scu-PA-32k was 23-fold higher than that of scu-PA (p less than 0.0005). In rabbits with a jugular vein clot prepared from human plasma, the thrombolytic potency of MA-15C5Hu/scu-PA-32k was 11-fold higher than that of scu-PA (p = 0.012). In baboons with an autologous whole blood clot in the femoral vein, the chimera had a 5-fold higher thrombolytic potency than scu-PA. In all three animal species, the clearance of the chimera was 10- to 27-fold reduced as compared to scu-PA. The specific thrombolytic activity (% lysis per micrograms/ml steady-state plasma u-PA antigen) was increased up to 7-fold with MA-15C5Hu/scu-PA-32k as compared with scu-PA, which is indicative of targeting of the chimera to the clot. No fibrinogen breakdown or alpha 2-antiplasmin depletion was observed during thrombolysis with the chimera. Thus, MA-15C5Hu/scu-PA-32k constitutes a recombinant chimeric plasminogen activator with a significantly enhanced thrombolytic potency in 3 different animal models of venous thrombosis.


Asunto(s)
Fibrinólisis/efectos de los fármacos , Activadores Plasminogénicos/farmacología , Animales , Anticuerpos Monoclonales/farmacología , Cricetinae , Modelos Animales de Enfermedad , Productos de Degradación de Fibrina-Fibrinógeno/inmunología , Humanos , Técnicas In Vitro , Papio , Activadores Plasminogénicos/farmacocinética , Embolia Pulmonar/tratamiento farmacológico , Conejos , Proteínas Recombinantes de Fusión/farmacocinética , Proteínas Recombinantes de Fusión/farmacología , Tromboflebitis/tratamiento farmacológico , Activador de Plasminógeno de Tipo Uroquinasa/farmacocinética , Activador de Plasminógeno de Tipo Uroquinasa/farmacología
14.
J Sleep Res ; 4(4): 199-201, 1995 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-10607159

RESUMEN

Behaviour in the 2-h period before sleep onset was evaluated in 90 subjects with normal sleep/wake habits using an anonymous self-report questionnaire. This determined the timing of events from the initial preparation for sleep. The nature of the pre-sleep environment, the level of physical activity, and patterns of feeding behaviour were recorded together with self-ratings of tiredness, mood and security. Estimated sleep duration and sleep quality were determined. Ninety of 120 subjects responded. Sleep 'preparatory latency', from the time of initial sleep preparation to sleep onset, was 77 +/- 48 min; bed time to sleep onset time (sleep latency) was 41 +/- 42 min; lights out to sleep onset latency was 26 +/- 45 min. The estimated total sleep time was 7 +/- 1 h. In the pre-sleep period, mean noise and illumination levels were low and environmental temperature rating was at the median point on a very cold-very hot scale (mean scale scores: 23, 28 and 50, respectively). All subjects went to the bathroom before going to bed. Twenty-five percent of normal subjects had a snack or meal in the 2-h period before sleep onset. Sixty percentage recorded setting an alarm, 27% had a bath or shower, 23% checked door locks or windows and 49% read in bed. Nine percent of subjects slept with a cat on the bed. Humans, like other animal species, show a complex behavioural sequence in the 2-h period before falling asleep. A constant environment with limited metabolic activity may predispose to thermoregulatory changes prior to sleep onset.

15.
Thromb Res ; 102(1): 61-9, 2001 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-11323016

RESUMEN

The matrix metalloproteinase (MMP) and fibrinolytic (plasminogen/plasmin) systems cooperate in many (patho)physiological processes requiring extracellular proteolysis. The effect of MMP-3 (stromelysin-1), MMP-7 (matrilysin), MMP-9 (gelatinase B) or MMP-12 (metalloelastase) on cellular fibrinolytic activity was studied with the use of smooth muscle cells (SMC) and fibroblasts derived from mice with specific inactivation of these genes. Activation of cell-bound plasminogen by two-chain urokinase-type plasminogen activator (tcu-PA) was not significantly different with SMC or fibroblasts from the gene-deficient mice (78% to 140% of wild-type). For all cell types, very limited conversion of plasminogen to angiostatin-like kringle-containing fragments was observed (< 3% of the total cell-bound plasminogen). Activation of plasminogen in solution by cell-associated tcu-PA was also comparable for SMC or fibroblasts of the different genotypes (54% to 160% of wild-type). In vitro SMC migration on scrape wounded collagen-coated surfaces was comparable for wild-type, MMP-7(-/-), MMP-9(-/-) and MMP-12(-/-) SMC, but was significantly reduced for MMP-3(-/-) SMC (P < .005 vs. wild-type). Serum-free conditioned medium of MMP-3(-/-) and MMP-7(-/-) SMC or fibroblasts induced similar lysis of fibrin films as wild-type cells. These findings indicate that several interactions that have been described between these MMPs and the plasminogen/plasmin system in a purified system do not significantly affect plasmin-mediated cellular fibrinolytic activity under cell culture conditions.


Asunto(s)
Fibrinólisis/efectos de los fármacos , Metaloproteinasas de la Matriz/deficiencia , Metaloproteinasas de la Matriz/farmacología , Animales , Células Cultivadas/efectos de los fármacos , Células Cultivadas/metabolismo , Quimiotaxis/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Humanos , Metaloproteinasas de la Matriz/genética , Ratones , Ratones Noqueados , Músculo Liso/citología , Plasminógeno/efectos de los fármacos , Plasminógeno/metabolismo , Activador de Plasminógeno de Tipo Uroquinasa/farmacología , Heridas y Lesiones/patología
16.
Thromb Res ; 65(3): 421-38, 1992 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-1631805

RESUMEN

K1K2Pu, a recombinant t-PA/u-PA chimera with increased thrombolytic potency in animal models of venous and arterial thrombosis, which consists of amino acids 1 to 3 and 87 to 274 of human tissue-type plasminogen activator (t-PA) and amino acids 138 to 411 of human single chain urokinase-type plasminogen activator (scu-PA), was produced and conditioned for use in patients. Chinese hamster ovary cells were transfected with an expression plasmid containing the K1K2Pu cDNA, high producer cell lines were selected and scaled up in 800 cm2 roller bottles, and 350 ml conditioned cell culture medium was harvested 3 to 7 times at 2 to 5 day intervals. Batches of 21 +/- 4 liter (mean +/- SD, n = 28) containing 1.8 +/- 0.6 mg/l of K1K2Pu related antigen were purified by chromatography on Copper chelate-Sepharose and immunoadsorption on an insolubilized murine monoclonal antibody (MA-1C8). Yields were 8.6 +/- 3.4 mg K1K2Pu per batch with a specific activity of 83,000 +/- 44,000 IU/mg. The final material, obtained at a concentration of approximately 0.7 mg/ml, was dialyzed against 0.3 M NaCl, 0.02 M Tris-HCl buffer, pH 7.5, containing 0.01% Tween 80 and 10 KIU/ml aprotinin. It was homogeneous on SDS-PAGE, contained 6.5 +/- 6.9 percent two chain material and the contamination with murine monoclonal antibody was less than 0.1 percent. After filtration of pools of 3 to 5 selected batches on 0.22 microns Millipore filters the material was sterile and virus free by routine screening; it was obtained at a concentration of approximately 0.5 mg/ml with a specific activity of 110,000 +/- 16,000 IU/mg (mean +/- SD, n = 3) and an endotoxin content of 0.5 to 7 units/mg. Bolus injection at a dose of 1 mg/kg in mice did not produce weight loss within 8 days. Thus, this material appears to be suitable for the investigation on a pilot scale of the pharmacokinetic and thrombolytic properties of K1K2Pu in patients with thromboembolic disease.


Asunto(s)
Fibrinolíticos/aislamiento & purificación , Activadores Plasminogénicos , Proteínas Recombinantes de Fusión/aislamiento & purificación , Activador de Tejido Plasminógeno/aislamiento & purificación , Activador de Plasminógeno de Tipo Uroquinasa/aislamiento & purificación , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Células CHO , Cricetinae , ADN/genética , Fibrinolíticos/farmacología , Fibrinolíticos/toxicidad , Humanos , Ratones , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Ingeniería de Proteínas , Proteínas Recombinantes de Fusión/farmacología , Proteínas Recombinantes de Fusión/toxicidad , Terapia Trombolítica , Activador de Tejido Plasminógeno/genética , Activador de Tejido Plasminógeno/farmacología , Activador de Tejido Plasminógeno/toxicidad , Activador de Plasminógeno de Tipo Uroquinasa/genética , Activador de Plasminógeno de Tipo Uroquinasa/farmacología , Activador de Plasminógeno de Tipo Uroquinasa/toxicidad
17.
Drug Alcohol Depend ; 49(1): 55-60, 1997 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-9476700

RESUMEN

This preliminary report is the first demonstration of the acute effects of diacetylmorphine (heroin) administration on functional activation in the human brain using functional magnetic resonance imaging (fMRI). Four opiate addicts who received regular prescriptions for heroin, underwent fMRI using a visual activation paradigm before and after a dose of 30 mg heroin. All four showed a decrease after the heroin dose in the extent of significant activation. This method shows promise for sequential scanning to determine brain activity in response to different drugs and routes of drug administration.


Asunto(s)
Encéfalo/anatomía & histología , Encéfalo/fisiología , Dependencia de Heroína/orina , Imagen por Resonancia Magnética/métodos , Estimulación Luminosa , Abuso de Sustancias por Vía Intravenosa/orina , Enfermedad Aguda , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oxígeno/sangre , Factores de Tiempo
18.
Parkinsonism Relat Disord ; 3(2): 103-7, 1997 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18591063

RESUMEN

Neuropsychiatric side effects often complicate anti-Parkinsonian therapy and pose a significant problem in the optimal management of idiopathic Parkinson's disease. Several publications report a relative lack of neuropsychiatric side effects in Parkinsonian patients treated with subcutaneous apomorphine. To investigate this further, we have used subcutaneous apomorphine to treat 12 non-demented IPD patients with previous oral drug-related neuropsychiatric problems. Treatment with apomorphine allowed alteration of anti-Parkinsonian medication and led to the abolition or reduction of neuropsychiatric complications in all patients. The mechanism remains unclear but may be due, in part, to a reduction in oral medication or a psychotropic action of apomorphine, possibly due to the piperidine moiety in its structure, or both.

19.
Parkinsonism Relat Disord ; 2(2): 63-7, 1996 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18591020

RESUMEN

We have performed proton magnetic resonance spectroscopy centred on the putamen contralateral to the worst affected side in 10 patients with idiopathic Parkinson's disease (PD) and motor response fluctuations and seven age matched healthy controls. In PD, there was striking reduction in the N-acetylaspartate (NAA) and creatine and NAA/choline ratios compared to controls. This pilot study provides in vivo evidence of striatal neuronal dysfunction in PD and further studies are in progress to establish if the observed changes are due to the disease process itself or due to chronic levodopa therapy.

20.
J Affect Disord ; 134(1-3): 226-34, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21684610

RESUMEN

BACKGROUND: Recent research indicates that different couple and family interventions are effective in the treatment of depressed patients. However, how these psychosocial interventions work, has been less well investigated. In order to better understand the underlying treatment processes, helpful treatment experiences of depressive patients and their partners were examined in a multi-family therapy group. METHOD: 24 patients hospitalized for depression and 20 partners participated in this study. Therapeutic factors were assessed using an open-ended questionnaire. Responses were analyzed using interpretative phenomenological approach (IPA). RESULTS: Eight recurring therapeutic factors were reported by both the patients and their partners: (1) Presence of others, (2) cohesion and understanding, (3) self-disclosure, (4) openness, (5) discussion, (6) insights, (7) observational experiences and (8) guidance from the therapist. LIMITATIONS: Results were not fed back to the participants following analysis and only therapeutic factors that operate on a conscious level could be identified. CONCLUSIONS: Several important therapeutic factors were identified in multi-family therapy groups for depression. These factors help to gain understanding into the processes, which should be emphasized in treatment and ought to be explored in future outcome and process research.


Asunto(s)
Terapia Familiar , Procesos Psicoterapéuticos , Adulto , Comunicación , Depresión , Trastorno Depresivo/psicología , Trastorno Depresivo/terapia , Trastorno Depresivo Mayor , Femenino , Humanos , Masculino , Persona de Mediana Edad , Autorrevelación , Encuestas y Cuestionarios
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