APATÍA ANTE EL DOLOR AJENO.

Quiero compartir este importante comentario del doctor Marco Vargas, JEFE DE La Unidad de Trauma del Hospital Nacional de Niños, el cual sería de mucha utilidad enviar a familiares y amigos, a mi parecer este es un mensaje que si deben recibir todos nuestros contactos de correo.

Lo Sentimos Mucho...Nos disculpan por favor La noche del pasado jueves, eran cerca de las 6 pm cuando un carro de bomberos verde limón y un par de motorizados de la policía de tránsito irrumpieron su paz mientras viajaban por la ruta número 1 (San José-Alajuela).

Cientos de personas abrieron un ¨túnel¨ entre los vehículos para poder avanzar, sin saberlo ustedes en esa caravana viajaban dos Policías de Tránsito, Carol y Oscar,  dos técnicos en emergencias del Cuerpo de Bomberos Rubén y Diego, un enfermero Arnaldo y yo.

Durante catorce minutos, justo detrás de ellos vimos a los policías ¨luchar¨ tenazmente contra el flujo vehicular, atascado a más no poder en la ruta hacia Alajuela, ellos, únicamente con su cuerpo como chasis y sus motocicletas como vehículo giraban órdenes y señalaban hacia dónde dirigirse a cada uno de los conductores que con nosotros interactuaron, todo para lograr un pequeño espacio de cerca de tres metros para que nuestro vehículo de rescate pudiera avanzar.

Fuimos testigos como la mayoría de los conductores acataron prontamente sus órdenes, vimos también a quienes les gritaron sus más profundas maldiciones, otros retaron su pericia como conductores y conocedores de que el objetivo final, de llevar un vehículo a puerto es más importante que una acción intermedia, en muchas ocasiones en lo que parecía un acto intencional bloquearon nuestro paso o peor aún ¨echaron¨ sus vehículos en contra de estos dos policías amenazando su vida e integridad,…………..por qué?????  Nunca lo entenderé.

Nuestro viaje se inició con una llamada de emergencia del Hospital de Upala, a ese centro había llegado un pequeño de menos de un año de edad críticamente enfermo por un evento relacionado a una colisión con objeto fijo.

Los miembros de La Cruz Roja atendieron su condición inicial, le llevaron a este centro y ahí muchos profesionales y personal de apoyo dio todo lo que podía y sabía para atender a este bebe.

Un par de pilotos despegaban cerca de las cinco de la tarde hacia Upala y el control de tierra monitoreaba cada detalle rogando por que sus compañeros pudieran salvar la tormenta que tenían que atravesar, todos ellos miembros del Servicio de Vigilancia Aérea.

Un médico y una enfermera se adosaban al interior de un pequeño avión para poder asistir a gran altura a este niño, sus familias también oraban para que todos llegaran vivos a tierra, nuevamente.

Periodistas nos acompañaron, en su labor, se han convertido en compañeros de su noticia y muchísimos de ellos han cruzado la frontera de volverla, de alguna forma,  personal y nos llaman para conocer como sigue aquel niño o niña que vieron en un momento agudo de su vida.

Todos en un tiempo espacio estábamos congelados en una acción, atender a un pequeño gravemente enfermo.

Finalmente, llega el avión y el ruido cósmico acelera nuestro cerebro, se abre la puerta y se vierte en un pequeño decenas de años de entrenamiento y estudio, y, empieza la angustia, realmente esta muy enfermo.

A la distancia, menos de veinte kilómetros  delante de nosotros un complejo grupo de profesionales nos esperan para continuar nuestra labor de reanimación crítica,  todos ellos se han comunicado con nuestro equipo en múltiples ocasiones para que la ejecución de su trabajo esté puntualmente sincronizado, sin embargo, nuevamente tenemos que cruzar un enjambre de vehículos que tienen un destino diferente al nuestro.

Otra vez, es una lucha por cada centímetro de autopista. Nuevamente lucha cuerpo a cuerpo, con franca desventaja.

Si por al menos un segundo, aquel conductor que nos ¨tiró¨ su camión a nosotros y a la mujer policía cerca del aeropuerto pudiera pensar que quizá su hijo era quien llevábamos en nuestra cabina, o tal vez un hermano o su padre, no habría detenido todo el tránsito solo para que durásemos un segundo menos……?

Finalmente llegamos, desgraciadamente nunca tuvimos una oportunidad sus lesiones eran terminales.

Hoy, muchas horas después, como Director de la Unidad de Trauma Hospital Nacional de Niños tengo la obligación de agradecer a todos aquellos que lucharon a nuestro lado por este pequeño bebe, es un orgullo y placer servir al país con hombres y mujeres como ustedes.

Hoy no es mas vulnerable ese par de oficiales que luego de batirse en lucha, dejaron caer sus lágrimas cuando al oído me correspondió comunicarles que nuestro paciente había muerto.

No lo son ellos como tampoco el personal que durante ocho horas, hasta las tres am esperó a la madre para poder decírselo de frente y que ella no tuviera que leerlo en un periódico Perdón a todos aquellos que nuestras sirenas y ¨cuerno¨ interrumpieron su paz relativa mientras conducían hacia y desde Alajuela, lo haremos todas las veces que seamos llamados al deber, ahora saben el por qué Y, ahora que lo saben, quizá quieran ayudar a los policías, bomberos, cruzrojistas y otros miembros de primera respuesta que a diario piden un pequeño espacio, de menos de tres metros de ancho, para salvar una vida, quizá podría ser la de un ser muy amado por usted

Dr. Marco V. Vargas S

Director Unidad de Trauma Hospital Nacional de Niños

El robo del conocimiento indígena, promovido por nuestros políticos.

les invito a ver el video de la UCR sobre el tema

Documental producido por la Unidad de Producción Audiovisual de la Vicerrectoría de Acción Social (Universidad de Costa Rica), que analiza el robo de los conocimientos tradicionales en los países pobres por parte de grandes corporaciones farmacéuticas. Dirección: Pablo Ortega/Edición: Melissa Rivera/Cámara: Giuseppe Cirotti & Sergio Madrigal/Animación 3D: Felipe Molina/Música: Grupo Indígena Jirondai

Es el dinero de la industria la raíz de los conflictos de interés en la investigación biomédica?

http://upenn.academia.edu/ArthurCaplan/Papers/610861/Is_industry_money_the_root_of_all_conflicts_of_interest_in_biomedical_research


Interesante artículo sobre ética e investigación biomédica.

Parkinsonismo por interferón alfa en paciente hemofílico con hepatitis C.

S.B.J.A Masculino d 46 año sin antecedente de toxicomanías AQ de cirugía lingual, extirpación de pólipo del colon, artroscopía de rodilla derecha. Portador de hemofilia leve, Hepatitis C adquirida  en su juventud pos infusión del Factor VIII de la coagulación, trombosis venosa profunda de la pierna izquierda, por la cual usa medias elásticas. Antecedentes familiares positivos por DM, HTA, Accidente vascular cerebral en el padre, Ca de mama en la madre, Ca de próstata en dos tíos. Cardiopatía isquémica en dos tíos.

Recibió tratamiento por hepatitis C con ribavirina mas interferón alfa en dos ocasionas, negativizando las cargas virales. Recibió el último ciclo de tratamiento a finales del 2009.   Seis meses después nota brincos involuntarios en la pierna derecha (mioclonías) y temblor de reposo; días después el temblor se le pasa a la mano derecha. No ha perdido fuerza. No tiene dificultad para incorporarse o darse vuelta en la cama. Le molesta el conducir auto, si no oprime el acelerador. No le molesta en la marcha. Sialorrea (-) trastornos de la voz leves según su esposa (disprosodia).

 La exploración física general y neurológica revelo: 108/69 con 79 de pulso. Peso:

Normofacies, cae (conductos auditivos externos) y fondo de ojo nls, pares nls, Signo de Meyerson positivo y de Jendricson en MSD   , fuerza , reflejos y sensibilidad simétrica. Temblor de reposo de mediana frecuencia en miembros derechos, el cual aumenta durante la marcha, disminución de sincinesias en MSD durante la marcha, Romberg ausente, cerebelo nl.  CsPsLs core rítmico, abdomen negativo.

El Paciente fue clasificado como Parkinsonismo posiblemente secundario al uso del interferón alfa (ver bibliografía) Y se inició tratamiento con una mescla de levodopa-carbidopa de liberación controlada, levodopa-carbidopa de liberación rápida y selegiline, agonista dopaminérgica. Se mantuvo el tratamiento de base de su presión arterial: Enalapril de 20 mg e hidroclorotiazida. En consultas sub siguientes se regularon las dosis de la medicación antiparkinsoniana, bajo el principio de “usar la menor dosis que nos dé el mejor efecto” sustituyendo la selegiline por bromocriptina, debido al costo del primer medicamento. Además  se instruyó al paciente con las indicaciones apropiadas de dieta para las personas parkinsonianas. Se espera en seis meses, reducir gradualmente la medicación y re evaluar clínicamente. Ya que se han reportado casos de reversibilidad de los síntomas.

Comentario: El uso del Interferón alfa no es frecuente en nuestro medio y se tiene muy poca experiencia en el manejo de las complicaciones neurológicas que se han descrito en la literatura médica.

Como todo tratamiento se debe evaluar el riego /beneficio que se obtiene en un determinado paciente para recomendar el tratamiento. Y se debe conseguir la autorización del paciente (consentimiento informando)  de previo del  paciente y/o familiares en relación a los posibles riesgos secundarios. En la literatura que se cita en la bibliografía adjunta, se informa de que algunos de estos casos remiten al suspender el medicamento neurotóxico , en otros no; es frecuente en la clínica, observar que medicamentos que producen parkinsonismo, puedan “sacar a flote” los síntomas de una enfermedad que de todos modos se iba a manifestar en el tiempo, un ejemplo de ello es la desaparición de síntomas parkinsonianos por meses luego de suspender el medicamento neurotóxico para luego iniciar con sintomatología clásica de enfermedad de Parkinson.

Glosario:

Disprosodia: pérdida de la acentuación normal al hablar.

Agonista: Medicamento que refuerza la acción de otro.

Jendricson: al rotar pasivamente la muñeca, se nota al pedirle al paciente que meta y saque la lengua en forma repetida o haga otro tipo de movimiento voluntario,  un aumento del tono muscular en rueda dentada.

Mioclonías: contracción brusca e involuntaria  de un músculo, que produce desplazamiento de la región o miembro afectado.

Romberg: Signo que nos permite evaluar si los receptores de posición del cuerpo, están enviando adecuadamente sus señales a través de las vías somestésicos hasta los centros del equilibrio, principalmente el cerebelo.

Sialorrea: excesiva e involuntaria salida de saliva por la boca

Signo de Meyerson ( incapacidad para impedir voluntariamente el parpadeo con los ojos abiertos, mientras se le percute con un dedo el entrecejo o glabela)

Sincinesias: movimientos de los brazos durante la marcha, importantes para mantener el equilibrio.

Bibliografía: Fuente Pub Med.  http://www.ncbi.nlm.nih.gov/pubmed

1. Eur J Gastroenterol Hepatol. 2010 May;22(5):628-31.

Parkinsonism in patients with chronic hepatitis C treated with

interferon-alpha2b: a report of two cases.

Kajihara M, Montagnese S, Khanna P, Amodio P, Schapira AH, Dusheiko GM, Morgan MY.

Centre for Hepatology, Department of Medicine, University College London Medical School, University College London, London, UK.

Details of two patients with chronic hepatitis C infection who developed features of Parkinsonism when treated with IFN-alpha2b and ribavirin are reported. The symptoms resolved when treatment was discontinued in one patient but not in the other. Physicians should be alert to the possibility that drug-related Parkinsonism may complicate treatment of hepatitis C infection with antiviral agents; the agent most likely responsible is IFN-alpha2b. Prompt withdrawal of treatment is mandatory but does not always guarantee reversal of the parkinsonian features.  PMID: 20075741  [PubMed - indexed for MEDLINE]

2. Arq Neuropsiquiatr. 2009 Sep;67(3A):715-6. Interferon-induced Parkinsonism in a patient with chronic hepatitis C.

Almeida CM, Galvão Mde L, Ferreira PL, Braga WS. Neurology Department, Fundação de Medicina Tropical do Amazonas, Brazil. acrmauri@ig.com.br  PMID: 19722060  [PubMed - indexed for MEDLINE]

3. Brain Behav Immun. 2009 Jan;23(1):55-63. Epub 2008 Jul 17. Peripheral cytokines profile in Parkinson's disease.

Reale M, Iarlori C, Thomas A, Gambi D, Perfetti B, Di Nicola M, Onofrj M. Department of Oncology and Neuroscience, University G. D'Annunzio Chieti-Pescara,Italy. mreale@unich.it

Higher levels of proinflammatory cytokines are found in Parkinson's disease (PD) patient's brains and inflammation is thought to be a major contributor to the neurodegeneration. During the inflammatory process, microglial release of pro inflammatory cytokines act on the endothelium of blood-brain barrier (BBB) cells to stimulate upregulation of adhesion molecules. Consequently, this up regulation leads to the recruitment of passing T cells and monocytes, which express the counter receptors, that then go on to release more cytokines [Whitton, P.S., 2007. Inflammation as a causative factor in the etiology of Parkinson's disease, Br. J. Pharmacol. 50, 963-976; Kortekaas, R., Leenders,K.L., Van Oostrom, J.C., Vaalburg, W., Bart, J., Willemsen, A.T., Hendrikse, N.H., 2005. Blood-brain barrier dysfunction in parkinsonian midbrain in vivo, Ann. Neurol. 57, 176-179]. In addition, a systemic inflammatory response results in the production of cytokines which circulate in the blood and communicate with neurons within the brain. Thus, a central inflammatory reaction interacts with peripheral blood mononuclear cells (PBMCs) modulating immune activity. The present study investigates levels of production and expression of cyto/chemokines by PBMCs in PD patients. Basal and LPS-induced levels of MCP-1, RANTES, MIP-1alpha, IL-8, IFNgamma, IL-1beta and TNFalpha were significantly higher in PD patients than in HC subjects (p<0.001), as determined by RT-PCR and Elisa methods. Cyto/chemokine levels were significantly correlated with UPDRS III and H/Y stage (p<0.001). The Pearson's correlation coefficient (R) was also used to assess the strength of the relationship between NF-kappaBp65 levels and all studied cyto/chemokines and between NF-kappaBp65, UPDRS III and H/Y score in PD patients. The overall results strengthen and extend the knowledge of the peripheral dysregulation in the cytokine network associated with PD.

PMID: 18678243  [PubMed - indexed for MEDLINE]

4. Neurosci Lett. 2008 Aug 22;441(2):158-62. Epub 2008 Jun 19. Serum interleukin (IL-2, IL-10, IL-6, IL-4), TNFalpha, and INFgamma concentrations are elevated in patients with atypical and idiopathic parkinsonism.

Brodacki B, Staszewski J, Toczyłowska B, Kozłowska E, Drela N, Chalimoniuk M,Stepien A. Department of Neurology, Military Institute of the Health Services, Warsaw,Poland.

We investigated serum levels of interleukin (IL)-2, IL-10, IL-6, IL-4, TNFalpha, INFgamma in 7 patients with atypical parkinsonism (AP), 31 idiopathic PD (iPD)patients, 17 idiopathic PD with cardiovascular risk factor (iPD-CVRF) patients, and 20 age-matched controls (healthy, non-parkinsonian patients). Cytokine concentrations were measured using the Becton Dickinson (BD) human Th1/Th2 Cytokine kit II with a flow cytometry system. The concentrations of IL-2, IL-10, IL-4, IL-6, TNFalpha, and INFgamma were detectable in the serum from all groups, including the control. Increased serum IL-2, IL-10, IL-4, IL-6, TNFalpha, and INFgamma concentrations were found in all groups of parkinsonian patients, as compared to the control group. The highest elevations of serum IL-2, IL-4, IL-6, TNFalpha, and INFgamma concentrations were observed in AP patients, as compared to the iPD and iPD-CVRF groups. However, the serum IL-6 concentration was higher in the iPD-CVRF group than in the iPD group. The IL-10 level was significantly higher in all groups of PD patients relative to the control group, but was the lowest in the serum from the AP patients. Moreover, the serum levels of lipid peroxidation products were enhanced 2.1- and 1.5-fold in AP and both iPD groups, respectively. These results argue in favor of the involvement of immunological events in the process of neurodegeneration in AP and PD.

PMID: 18582534  [PubMed - indexed for MEDLINE]

5. Eur J Intern Med. 2008 Jul;19(5):370-1. Epub 2007 Nov 28.

Recovery after L-DOPA treatment in peginterferon and ribavirin induced

parkinsonism. Bersano A, Aghemo A, Rumi MG, Ballabio E, Candelise L, Colombo M. Department of Neurological Sciences Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, 7 IRCCS, Via F. Sforza 35, Università degli Studi di Milano, Milano, Italy. anna.bersano@unimi.it

BACKGROUND: Hepatitis C virus (HCV) chronically infects approximately 2% of the European population. Antiviral therapy with pegInterferon-alpha (PegIFN) and ribavirin (Rbv) is the standard of care, leading to HCV eradication in roughly 50% of patients. IFN-based therapy has been associated with high rates (20%) of central nervous system side effects, but only a few case reports exist on extrapyramidal side effects. RESULTS: We report a 64-year-old man developing Parkinsonism during PegIFN alfa-2a and ribavirin therapy for chronic hepatitis C. No improvement was observed after treatment discontinuation. Therefore, on the basis of previous clinical and experimental reports, levodopa-benserazide treatment was started.

After substantial improvement, symptoms relapsed following drug tapering. CONCLUSIONS: This is the first case of Parkinsonism in a Caucasian patient receiving PegIFN/Rbv therapy. The rapid and significant improvement of symptoms obtained in our patient with levodopa-benserazide, suggests that this therapy could be considered as first line symptomatic treatment.

PMID: 18549943  [PubMed - indexed for MEDLINE]

6. Brain Res. 2008 Jun 27;1217:203-12. Epub 2008 Apr 10.

Cytokines disrupt intracellular patterns of Parkinson's disease-associated proteins alpha-synuclein, tau and ubiquitin in cultured glial cells. Bick RJ, Poindexter BJ, Kott MM, Liang YA, Dinh K, Kaur B, Bick DL, Doursout MF, Schiess MC. Department of Pathology and Laboratory Medicine, University of Texas Medical

School at Houston, Texas 77030, USA. Roger.J.Bick@uth.tmc.edu

The purpose of this study was to determine the effects of specific

proinflammatory cytokines interleukin-6 (Il-6), interleukin-1beta (Il-1beta), interferon-gamma (IFN), and tumor necrosis factor-alpha (TNFalpha), on content and distribution of alpha-synuclein (alpha-synuclein), tau and ubiquitin in human derived cultured glial cells. Exposure paradigms mimicked acute (2 h), intermediate (18 h) and prolonged time frames (96 h); consisting of single or repeated low doses (10 ng/ml) or high doses (50 ng/ml), consistent with either

mild or serious systemic infectious/inflammatory responses. Images of

intracellular protein content and distribution were reconstructed from emission patterns generated by fluorescence deconvolution microscopy. Minor alterations were seen in protein content with IFN; Il-1beta decreased alpha-synuclein and tau at 18 and 96 h; TNFalpha inversely reduced alpha-synuclein and increased ubiquitin content. Combinations of Il-1beta and IFN produced a robust increase of alpha-synuclein and tau at 2 h. Consecutive low doses of Il-6 produced only minor increases in alpha-synuclein and ubiquitin after 4 h, whereas a single high dose resulted in major increases for all three proteins over the first 18 h. Protein localization patterns were distinctly different and were altered dependent upon cytokine treatment. A high dose exposure (2 x 50 ng/ml) with Il-6 and IFN demonstrated that protein increases and dispersals could be sustained and that the normal perinuclear tau and peripheral alpha-synuclein patterns were

disrupted. These results support the postulate that specific cytokines affect temporal protein changes with concomitant pattern disruptions, possibly reflecting a mechanism of cell dysfunction in Parkinson's degeneration.

PMID: 18501880  [PubMed - indexed for MEDLINE]

7. J Neuroinflammation. 2008 Feb 27;5:8.

Neuroinflammation mediated by IL-1beta increases susceptibility of dopamine neurons to degeneration in an animal model of Parkinson's disease.

Koprich JB, Reske-Nielsen C, Mithal P, Isacson O.

Center for Neuroregeneration Research, Harvard Medical School/McLean Hospital, Belmont, MA 02478, USA. jkoprich@mclean.harvard.edu

BACKGROUND: The etiology of Parkinson's disease (PD) remains elusive despite identification of several genetic mutations. It is more likely that multiple factors converge to give rise to PD than any single cause. Here we report that inflammation can trigger degeneration of dopamine (DA) neurons in an animal model of Parkinson's disease.

METHODS: We examined the effects of inflammation on the progressive 6-OHDA rat model of Parkinson's disease using immunohistochemistry, multiplex ELISA, and cell counting stereology.

RESULTS: We show that a non-toxic dose of lipopolysaccharide (LPS) induced secretion of cytokines and predisposed DA neurons to be more vulnerable to a subsequent low dose of 6-hydroxydopamine. Alterations in cytokines, prominently an increase in interleukin-1beta (IL-1beta), were identified as being potential mediators of this effect that was associated with activation of microglia. Administration of an interleukin-1 receptor antagonist resulted in significant

reductions in tumor necrosis factor-alpha and interferon-gamma and attenuated the

augmented loss of DA neurons caused by the LPS-induced sensitization to

dopaminergic degeneration.

CONCLUSION: These data provide insight into the etiology of PD and support a role

for inflammation as a risk factor for the development of neurodegenerative

disease.

PMCID: PMC2292163

PMID: 18304357  [PubMed - indexed for MEDLINE]

8. Mov Disord. 2005 May;20(5):569-73.

Investigation of genes coding for inflammatory components in Parkinson's disease. Håkansson A, Westberg L, Nilsson S, Buervenich S, Carmine A, Holmberg B, Sydow O, Olson L, Johnels B, Eriksson E, Nissbrandt H. Department of Pharmacology, Sahlgrenska Academy at Göteborg University, Göteborg, Sweden. anna.hakansson@pharm.gu.se

Several findings obtained recently indicate that inflammation may contribute to the pathogenesis in Parkinson's disease (PD). Genetic variants of genes coding for components involved in immune reactions in the brain might therefore influence the risk of developing PD or the age of disease onset. Five single nucleotide polymorphisms (SNPs) in the genes coding for interferon-gamma (IFN-gamma; T874A in intron 1), interferon-gamma receptor 2 (IFN-gamma R2; Gln64Arg), interleukin-10 (IL-10; G1082A in the promoter region), platelet-activating factor acetylhydrolase (PAF-AH; Val379Ala), and intercellular adhesion molecule 1 (ICAM-1; Lys469Glu) were genotyped, using pyrosequencing, in 265 patients with PD and 308 controls. None of the investigated SNPs was found to be associated with PD; however, the G1082A polymorphism in the IL-10 gene promoter was found to be related to the age of disease onset. Linear regression showed a significantly earlier onset with more A-alleles (P = 0.0095; after Bonferroni correction, P = 0.048), resulting in a 5-year delayed age of onset of

the disease for individuals having two G-alleles compared with individuals having two A-alleles. The results indicate that the IL-10 G1082A SNP could possibly be related to the age of onset of PD.

PMID: 15648059  [PubMed - indexed for MEDLINE]

9. Clin Neuropharmacol. 2004 May-Jun;27(3):105-7.

Acute dystonia during pegylated interferon alpha therapy in a case with chronic hepatitis B infection. Atasoy N, Ustundag Y, Konuk N, Atik L.

Department of Psychiatry, Zonguldak Karaelmas University, Faculty of Medicine, Kozlu/Zonguldak, Turkey. nurayulus@yahoo.com

Interferon (IFN) is the most widely prescribed drug of choice for chronic

hepatitis B infection, which is a common health problem in our country. Therapy with IFN-alpha may be associated with a number of neuropsychiatric symptoms, such as Parkinsonism, akathisia, seizure, and depressive disorders. In this case report, we present clinical and laboratory findings of a case with chronic hepatitis B that developed acute dystonia soon after the first dose of pegylated interferon alpha. As far as we know, this is the first report in English

Literature indicating such an adverse effect of pegylated interferon alpha.

PMID: 15190230  [PubMed - indexed for MEDLINE]

10. Biomed Khim. 2003 Mar-Apr;49(2):208-12.

[Level of interferon-gamma, tumor necrosis factor alpha, and antibodies to them

in blood serum from Parkinson disease patients].

[Article in Russian] Gribova IE, Gnedenko BB, Poleshchuk VV, Morozov SG. 29 Municipal Hospital of Moscow Public Health Department, Gospitalnaya Square, 2, 111020, Moscow.

Serum levels of interferon-gamma (IF gamma), tumor necrosis factor alpha (TNF alpha) and autoantibodies (a-AT) to these cytokines were investigated in patients with Parkinson's disease (PD). The increased levels of TNF alpha (50%) and IF gamma (35%) were found in PD patients. There was close correlation between the serum level of TNF alpha and the manifestation of neurological symptoms (r = 0.434; p < 0.05), and between levels of IF gamma and the duration of this disease

(r = 0.4511, p < 0.05) and patients age as well (r = 0.4358; p < 0.05). There was increased level of a-AT to TNF alpha in PD patients versus healthy controls (130.3 +/- 11.92 and 105.3 +/- 4.62, respectively, p < 0.05). The combined increase of levels of a-AT to TNF alpha and IF gamma (r = 0.91, p < 0.01) close reverse correlation between duration of PD and levels of a-AT to TNF alpha and IF

gamma (r = 0.4644 and r = 0.606, respectively, p < 0.01) were also recognised. The data obtained suggest the involvement of TNF alpha and IF gamma into the pathological process during PD, which requires further investigation in this direction.

PMID: 14565085  [PubMed - indexed for MEDLINE]

11. Brain Res. 2003 Jul 18;978(1-2):104-14.

Mechanism of systemically injected interferon-alpha impeding monoamine

biosynthesis in rats: role of nitric oxide as a signal crossing the blood-brain barrier.

Kitagami T, Yamada K, Miura H, Hashimoto R, Nabeshima T, Ohta T.

Department of Biochemistry, Nagoya University Graduate School of Medicine, Tsuruma-cho, Showa-ku, Nagoya 466, Japan. tomtsu@med.nagoya-u.ac.jp

The serious and characteristic side effects of interferon-alpha (IFN-alpha)therapy on the central nervous system, resulting in such problems as affective disorders or parkinsonism, have led us to investigate the biochemical mechanism of the effects of IFN-alpha on the monoaminergic neurotransmitter system using an animal model (rats). We first examined the concentrations of tetrahydrobiopterin

(BH(4)) and monoamines in several regions of the brain after the intramuscular injection of IFN-alpha into rats; the levels of BH(4) and dopamine significantly decreased in the amygdala and raphe areas as compared with those of the controls. Based on these results, we further examined the concentrations of BH(4) and nitrite (NO(2)(-)) plus nitrate (NO(3)(-)), metabolites of nitric oxide (NO), in

the amygdala and raphe areas after the intramuscular injection of IFN-alpha; the concentrations of both BH(4) and NO(2)(-)+NO(3)(-) significantly decreased as compared with the control. Furthermore, the addition of N(G)-monomethyl L-arginine, an inhibitor of NO synthase, after the injection of IFN-alpha restored the decreased levels of both NO(2)(-)+NO(3)(-) and BH(4) to control levels. As a result, nitric oxide induced by the intramuscular injection of IFN-alpha was found to cross the blood-brain barrier and suppress both tetrahydrobiopterin biosynthesis and dopamine production in the amygdala and raphe areas.

PMID: 12834904  [PubMed - indexed for MEDLINE]

12. Hawaii Med J. 2002 Mar;61(3):48, 57.

Parkinsonism associated with interferon alpha therapy for chronic myelogenous leukemia.

Sarasombath P, Sumida K, Kaku DA. UH School of Medicine, 1356 Lusitana St., 7th Fl., Honolulu, HI 96813, USA.

spichaya@hotmail.com

A 79 year-old man was treated with Interferon alpha for chronic myelogenous leukemia and developed severe parkinsonism that resolved after Interferon alpha was stopped. Carbidopa-levodopa was associated with early improvement, but discontinuation did not result in worsening of the parkinsonism.

PMID: 11965836  [PubMed - indexed for MEDLINE]

13. J Interferon Cytokine Res. 2001 May;21(5):273-8.

Neuropsychiatric effects and type of IFN-alpha in chronic hepatitis C.

Malaguarnera M, Laurino A, Di Fazio I, Pistone G, Castorina M, Guccione N,Rampello L.

Department of Internal Medicine and Geriatrics, University of Catania, Ospedale Cannizzaro, Via Messina 829, 95126 Catania, Italy. malaguar@mbox.unict.it

Chronic hepatitis is often associated with neuropsychiatric disorders. Interferon (IFN) is the drug most widely used to treat this disease, and its side effects,such as depression, often involve the central nervous system (CNS). Symptoms include a slowing down of psychomotor functions, loss of interest, frontal lobe dysfunction, parkinsonism, and delirium. The occurrence of these complications calls for dropping out of IFN treatment or for a significant dose reduction and

administration of antidepressants. Efficacy and side effects vary on the basis of the IFN type employed. The aim of our study was to evaluate if the frequency,form, and degree of depression induced are related to the type of IFN employed.We studied 96 patients with chronic hepatitis C. Our study series was divided into four groups according to the type of IFN-alpha administered. Depression

degree was clinically evaluated using the Hamilton Depression Rating Scale (HAM-D). All patients were tested before treatment and 1, 3, and 6 months (15 days after the end of treatment) later. Our results showed that the type of IFN used seemed to influence the depression onset rate, with the leukocyte type inducing the lowest level of depression. However, when a number of symptoms associated with the depression were considered, the results of other types of

IFN-alpha were found to be better. Use of the most suitable type of IFN-alpha could thus lead to more personalized treatment, with fewer side effects. The type of IFN used seems to influence the psychological side effects and the adaptation rate to therapy. It would be appropriate to choose the type of IFN on the basis

of a neuropsychiatric assessment carried out before treatment.

PMID: 11429157  [PubMed - indexed for MEDLINE]

14. Rinsho Shinkeigaku. 1997 Jan;37(1):54-6. [Parkinsonism in a patient receiving interferon alpha therapy for chronic hepatitis C].

[Article in Japanese] Mizoi Y, Kaneko H, Oharazawa A, Kuroiwa H.

Department of Neurology, General Ohta hospital.

We report a case of Parkinsonism due to interferon alpha (IFN alpha) therapy for chronic hepatitis C. A 51-year-old female received IFN alpha (Sumipheron@6 x10(6) IU), three times a week by intramuscular injection. Six months after the initiation of IFN alpha therapy, she noticed tremor of bilateral fingers, and was admitted to our hospital. Neurological examination revealed muscle rigidity, bilateral finger tremor, mild bradikinesia. Tremor was more extreme at posture at her than at rest. She was diagnosed as Parkinsonism, and carbidopa-levodopa therapy was effective. Attention must be paid to arkinsonism, when IFN alpha is administered.

PMID: 9146076  [PubMed - indexed for MEDLINE]

15. Neurosci Lett. 1994 Nov 7;181(1-2):61-4.

Immunohistochemistry using antibodies to alpha-interferon and its induced protein, MxA, in Alzheimer's and Parkinson's disease brain tissues. Yamada T, Horisberger MA, Kawaguchi N, Moroo I, Toyoda T.

Department of Neurology, School of Medicine, Chiba University, Japan.

The localization of alpha-interferon (alpha-IFN) and its induced protein, MxA, was examined in human brain tissues from neurologically normal, Alzheimer's disease (AD) and Parkinson's disease (PD) cases. In all cases, a few neurons in the superficial cortical layers and microglial cells in the white matter were stained with the antibody to alpha-IFN. In AD brains, white matter microglia were

intensely labeled for alpha-IFN and reactive microglia, such as those on senile plaques, were strongly positive for MxA protein. In PD, Lewy bodies in the substantia nigra were positive for MxA, but there was no staining for alpha-IFN in that region. These results suggest that increased expression of alpha-IFN in the white matter microglia and appearance of MxA protein in reactive microglia contribute to Alzheimer pathology. The staining of some Lewy bodies for MxA may

be indicative of a viral infection or other unknown factor.

PMID: 7898772  [PubMed - indexed for MEDLINE]

  

http://www.ncbi.nlm.nih.gov/pubmed