Actualización en enfermedad con cuerpos de Lewy / Update in Lewy body disease

La enfermedad con cuerpos de Lewy incluye 2 entidades que podrían ser consideradas variantes clínicas de una misma patología: la demencia con cuerpos de Lewy y la demencia en enfermedad de Parkinson. Con la finalidad de describir correctamente lo que sucede en la evolución de la enfermedad se divide el cuadro en etapa prodrómica y de demencia propiamente dicha. La primera está clínicamente representada por aquel período en el cual, si bien el paciente exhibe algunos signos y síntomas propios de la enfermedad, no reúne criterios de demencia. A pesar de ser difícil de definir y por carecerse todavía de contundentes datos clínicos y biomarcadores, se caracteriza principalmente por deterioro leve selectivo en función atencional ­ visuoespacial, trastorno del sueño REM y disautonomía‒. La segunda etapa está claramente caracterizada en los criterios de consenso del año 2005. Recientemente hemos publicado la validación de un instrumento llamado ALBA Screening Instrument, que permite diagnosticar con alta sensibilidad y especificidad la enfermedad aun en etapas tempranas y diferenciarla de otras patologías semejantes. La tomografía por emisión de positrones (PET) para transportador de dopamina es el procedimiento de referencia (gold standard) del diagnóstico. El tratamiento sintomático con anticolinesterásicos y neurolépticos atípicos favorece una buena evolución de la enfermedad y es fundamental tener en cuenta evitar medicamentos que pueden dañar gravemente a los pacientes como los anticolinérgicos y antipsicóticos típicos. Los avances en el diagnóstico y la difusión del impacto de esta enfermedad en la población contribuirán a generar mayores esfuerzos de investigación para hallar un tratamiento eficaz, preventivo o curativo o de ambas características. (AU)

Lewy body disease includes 2 entities that could be considered clinical variants of the same pathology: Dementia with Lewy bodies and Parkinson's disease Dementia. Two stages of the disease are described in this review, a prodromal stage and one of explicit dementia. The first one is clinically represented by that period in which, the patient exhibits some typical features of the disease, but not dementia criteria. Despite being difficult to define the prodromal stage and that strong clinical data and biomarkers are still lacking, there is evidence to characterize it mainly by mild selective impairment in attention and visuo-spatial function, REM sleep disorder and dysautonomia. The second stage is clearly characterized in the known consensus criteria of 2005. We have recently published the validation of an instrument called ALBA Screening Instrument which showed a high sensitivity and specificity for diagnosis of the disease even in the early stages. It´s useful to differentiate the disease from other similar pathologies. Positron Emission Tomography for dopamine transporter is the gold standard of diagnosis in life. Symptomatic treatment with anticholinesterases and atypical neuroleptics help patients in their evolution of the disease. Anticholinergics and typical antipsychotics are agents to avoid in the treatmen of the disease because can severely damage patients. Future advances in the diagnosis and dissemination of the knowledge of the disease will contribute to generate greater research efforts to find an effective preventive and / or curative treatment. (AU)

Pharmacological Treatments for Tinnitus / 한양의대학술지

Pharmacotherapy has been constantly chosen by the clinician among the available treatment options for tinnitus. Medications that have been prescribed off-label to treat tinnitus can be grouped into several categories: benzodiazepines, antidepressants, anticonvulsants, N-methyl-D-aspartate (NMDA) receptor antagonists, dopamine receptor modulators, muscle relaxants, and others. In this article, a wide variety of compounds once used in the treatment of tinnitus and evidenced by clinical trials are reviewed with respect to the mechanisms of action and the drug efficacy. Only a few of the various pharmacological interventions investigated have some beneficial effects against tinnitus: clonazepam, acamprosate, neramexan, and sulpiride. Sertraline and pramipexole were effective in subgroups of patients with psychiatric symptoms or presbycusis. However, no agents have been identified to provide a reproducible long-term reduction of tinnitus in excess of placebo effects. In rodent tinnitus models, L-baclofen, memantine, and KCNQ2/3 channel activators have been demonstrated to reduce tinnitus development. Limitation of the use of an effective high dosage during a longer treatment duration due to dose-dependent side effects of the centrally acting drugs may influence the results in clinical studies. More effective and safer innovative agents should be developed based on the further understanding of tinnitus neural mechanisms and valid animal models, and should be supported by improved clinical trial methodology. The management of tinnitus patients through a tailored treatment approach depending on the detailed classification of tinnitus subtypes will also lead to better treatment outcomes.

Síndrome de Cotard asociado a trastorno depresivo mayor con síntomas catatonicos: informe de caso / Síndrome de Cotard associada ao transtorno depressivo maior com sintomas catatonicos: relato de caso / Cotard Syndrome Associated to major depressive disorder with catatonic symptoms: case report

Catatonia is a neuropsychiatric syndrome with abnormal postures, mutism and stupor. Colombia has a prevalence of 11.4% of psychiatric patients. Objective: To discuss the clinical curse of a 34-year-old woman with major depressive disorder that presents to emergency department with nihilistic delirium and catatonic symptoms. Case presentation: A young woman with history of unipolar major depression with psychotic features was hospitalized nine months ago. She was medicated with a pharmacological treatment she did not remember. At admission, the patient had three days of bizarre behavior, mutism and negativism. Paraclinics and brain computer tomography did not report any abnormality or changes. Treatment began with benzodiazepine, which achieved full remission of catatonic symptoms. After this, she developed anhedonia, sadness and nihilistic delusions and was considered as a relapse of a previous depressive episode from nine months ago, associated with CotardÆs syndrome. Sertraline was added with gradual increase to 100mg and 5mg of olanzapine, getting a complete remission of psychotic and mood symptoms. Discussion: Affective disorders are most common cause of catatonia. There has already been a history of similar reports, but in few times these three entities were associated; this is the first case reported in Hospital Universitario de Santander, with informed consent. Conclusions: It is unusual for a depressed patient to present denial delusions and catatonic symptoms simultaneously; therefore this case is unusual and may contribute to literature. The catatonic symptoms make it difficult to explore other mental spheres, though they may be secondary to a medical condition, therefore, it is essential to dismiss organic pathologies and give initial treatment, so we can discover the underlying etiopsychopathology.

A catatonia é uma síndrome neuropsiquiatrica com posturas anormais, silêncio e estupor. A Colômbia tem uma prevalência de 11,4% de pacientes psiquiatricos. Objetivo: Discutir o caso clínico de uma mulher de 34 anos com uma história de transtorno depressivo maior que chega ao departamento de emergência com delírios niilistas e os sintomas catatónicos. Relato de caso: Foi relatado o caso de uma jovem adulta com transtorno depressivo maior e sintomas psicóticos que tinha sido hospitalizada nove meses antes, a quem deram alta com tratamento medicamentoso que ela não se lembrava. A paciente chegou ao pronto socorro do Hospital Universitário de Santander, apresentando três dias de um comportamento incomum, mutismo e negativismo. Exames laboratoriais e tomografia do crânio normal. O tratamento foi iniciado com uma benzodiacepina que a remeteu aos sintomas catatónicos. Posteriormente demonstrou anedonia, tristeza e delírios niilistas; considerou-se que seu estado correspondia a uma recorrência de episódio depressivo, começado nove meses antes, relacionado com a síndrome de Cotard. Gradualmente a paciente foi medicada com sertralina de 150,0 mg a 5,0 mg e olanzapina de 5.0 mg, obtendo a remissção dos sintomas afetivos e psicoticos. Discussão: A desordem afetiva é a causa mais comum de catatonia. Hß relatos semelhantes, embora poucos onde coexistam os três sintomas; este é o primeiro caso relatado no Hospital Universitário de Santander, com prévio consentimento informado. Conclusões: É incomum para uma pessoa deprimida ter delírios de negação e sintomas catatónicos simultaneamente, de modo que este caso, por ser único, gera novidade para a literatura. No caso, os sintomas catatónicos dificultam a exploração de outras esferas mentais e podem ser considerados secundários a uma condição médica, motivo pelo qual é essencial excluir causas orgânicas, trata-los prontamente e assim esclarecer a psicopatologia subjacente.

Novedosos agentes dopaminérgicos centrales derivados del 2-aminoindano-4,7 disustituido atípico. Síntesis y perfil farmacológico central / Novel central dopaminergic agents derived from atypical di-substituted 2-aminoindane-4, 7. Synthesis and central pharmacological profile

En las últimas décadas son muchos los compuestos con actividad dopaminérgica central que se han diseñado, sintetizado y evaluado farmacológicamente. A pesar de ello, no se ha logrado obtener un fármaco capaz de mejorar o curar las patologías que involucran la regulación dopaminérgica en el sistema nervioso central tales como la Enfermedad de Parkinson y la esquizofrenia, entre otras. Tomando en consideración el término de “farmacóforo atípico” y a partir del compuesto 5, se incorporó el fragmento aralquil y se sintetizaron los compuestos 10, 11, 13a-h y 14a-h. Tanto los compuestos 10 y 13a-h bajo su forma metoxilada como los compuestos 11 y 14a-h bajo su forma fenólica, fueron evaluados farmacológicamente para determinar su actividad agonística y antagonística sobre el sistema dopaminérgico central. Para ello se determinó el efecto de la inyección intracerebroventricular de dichos compuestos sobre el balance hidromineral y la conducta estereotipada en ratas. Los resultados de la evaluación farmacológica preliminar muestran una acción central a través de mecanismos dopaminérgicos, siendo que los compuestos 10, 11, 13d-h y 14a mostraron respuestas como agonistas, mientras que los compuestos 14b-h, tuvieron respuestas como antagonistas.

In recent decades, many compounds with central dopaminergic activity have been designed, synthesized and evaluated pharmacologically. However, it has not been possible to obtain a drug able to improve or cure diseases involving dopaminergic regulation in the central nervous system, such as Parkinson’s disease and schizophrenia, among others. Taking into consideration the term “atypical pharmacophore” and from the compound 5, the aralkyl fragment was incorporated, and the compounds 10, 11, 13a-h and 14a-h were synthesized. Both the compounds 10 and 13a-h under its methoxylated form and the compounds 11 and 14a-h under the phenolic form, were evaluated to determine their pharmacologically agonistic and antagonistic effects on central dopaminergic activity. For this, the effect of intracerebroventricular injection of said compounds on the hydromineral balance and stereotyped behavior in rats, was determined. The results of the preliminary pharmacological evaluation show a centrally acting action through dopamine mechanisms, in which the compounds 10, 11, 13d-h and 14a showed responses as agonists, whereas compounds 14b-h, had responses as antagonists.

Validación de un método analítico de determinación de dopamina por cromatografía líquida de alta resolución / Validation of analytical method for dopamine determination by high-performance liquid chromatography

INTRODUCCIÓN: la dopamina es una hormona endógena del grupo de las catecolaminas que se emplea como fármaco para simular la acción del sistema nervioso simpático, promueve el incremento de la frecuencia cardiaca y la presión arterial. Sin embargo; este medicamento presenta un alto potencial genotóxico y está asociado al tratamiento de enfermedades como la esquizofrenia y el Mal del Parkinson. Por tal motivo ha resultado de gran interés su determinación en las aguas residuales que emergen de su producción. OBJETIVO: validar un método para la cuantificación por cromatografía líquida de alta resolución de la dopamina presente en disoluciones acuosas. MÉTODOS: la validación se llevó a cabo empleando una columna RP-18 de 250 x 4,6 mm, 5 µm; fase móvil: NaH2PO4 al 1 por ciento/CH3OH (90/10); flujo: 1,0 mL/min y un detector ultravioleta visible a 280 nm. Se calcularon los límites de detección y cuantificación, y se evaluó la estabilidad del medicamento en las condiciones de análisis. RESULTADOS: se obtuvieron pruebas documentadas que demuestran que el método resultó ser lineal (r= 0,999 y r2= 0,998), exacto y preciso en el intervalo de 1 x 10-4 mol/L a 2 x 10-3 mol/L; además, fue selectivo frente a los posibles productos de degradación obtenidos mediante la ozonización. CONCLUSIONES: el método estudiado resulta lineal, preciso y exacto en el intervalo de concentraciones analizado, lo que permite la determinación de dopamina en solución acuosa(AU)

INTRODUCTION: dopamine is an endogenous hormone in the catecholamine group, which is used to simulate the sympathetic nervous system action and to raise the heart rate and the blood pressure. However, this drug has high genotoxicity and is associated with the treatment of diseases such as schizophrenia and Parkinson's disease. For this reason, the determination of dopamine in wastewaters coming from its production has been of great interest. OBJECTIVE: to validate a high performance liquid chromatography method for quantification of dopamine present in aqueous solutions. METHODS: the validation used a RP-18 250 x 4.6 mm 5 µm column, mobile phase: 1 percent NaH2PO4 /CH3OH (90/10), 1.0 mL/min flow rate and a visible ultraviolet detector at 280 nm. Detection limits and quantitation were estimated in addition to evaluating the drug stability under the analysis conditions. RESULTS: documented evidence showed that the method proved to be linear (r= 0.999 and r2= 0.998), accurate and precise in the range of 1 x 10-4 mol/L to 2 x 10-3 mol/L. This method was also selective against potential degradation products from ozonization. CONCLUSIONS: the studied method was linear, precise and accurate in the range of tested concentrations, allowing the dopamine determination in aqueous solutions(AU)

Impact of dopamine receptor modulation on reduced anxiety-like behavior in neonatal rats after hypoxic-ischemic brain damage / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To observe the long-term changes in anxiety-like behavior and tyrosine hydroxylase (TH) expression in the substantia nigra (SN) after hypoxic-ischemic brain damage (HIBD) in a neonatal rat model and to further explore the relationship between dopamine (DA) level and long-term anxiety-like behavior using the DA receptor (DAR) antagonist.</p><p><b>METHODS</b>Seven-day-old (P7) neonatal Sprague-Dawley (SD) rats were randomized into normal control, sham-operated, HIBD and HIBD+DAR antagonist groups. HIBD model was prepared by ligating the right common carotid artery and 8% hypoxia exposure. The rats in the sham-operated group were sham-operated and were not subjected to right common carotid artery ligation and hypoxia exposure. The DAR antagonist was injected intraperitoneally before and after inducing HIBD. The same amount of normal saline was given to the other three groups as a control. Anxiety-like behavior was evaluated by elevated plus maze test, and TH expression in the SN was measured by immunohistochemistry on P14, P21, and P28.</p><p><b>RESULTS</b>On P21 and P28, the time spent in the open arms and the percentage of open arms entries in the HIBD group were significantly increased compared with those in the normal control, sham-operated and HIBD+DAR antagonist groups (P<0.05); in addition, the HIBD+DAR antagonist group showed a significantly longer time spent in the open arms than the normal control group (P<0.05). On P14, P21, and P28, TH expression in the HIBD and HIBD+DAR antagonist groups was significantly lower than that in the normal control and sham-operated groups, and TH level in the HIBD group was significantly lower than that in the HIBD+DAR antagonist group (P<0.05).</p><p><b>CONCLUSIONS</b>DAR antagonist allows the restoration of anxiety-like behavior and alleviates the damage to dopaminergic neurons in SD rats after HIBD.</p>

Acamprosate-induced Extrapyramidal Symptoms in an Elderly Patient with Alcohol Dependence

Acamprosate reduces the craving for alcohol by decreasing glutamate activity and increasing gamma-aminobutyric acid (GABA) action in patients with alcohol dependence. Acamprosate has tolerable side effects that include diarrhea, headache, dizziness and pruritus. In this study, we report acamprosate-induced extrapyramidal symptoms in an elderly patient with no history of neurologic disease. Severe extrapyramidal symptoms developed two days after the administration of acamprosate and improved over one week after the acamprosate was stopped. Extrapyramidal symptoms are commonly associated with dopamine receptor antagonists. However, there have been several reports of extrapyramidal symptoms occurring with drugs targeting other systems, including GABA, glutamate and serotonin. Acamprosate may decrease dopamine levels in the ventral tegmental area mediated by glutamatergic action and thus cause extrapyramidal symptoms. We suggest that acamprosate carries the risk of causing extrapyramidal symptoms.

La intoxicación con cobre disminuye la sobrevida e induce alteraciones neurológicas en Drosophila melanogaster / Copper intoxication decreases lifespan and induces neurologic alterations in Drosophila melanogaster

La enfermedad de Wilson, es un trastorno hereditario autosómico recesivo causado por mutaciones del gen de la trifosfatasa de adenosina (ATP7B). Dicha mutación ocasiona intoxicación con cobre, generando manifestaciones clínicas por los efectos tóxicos del metal, principalmente a nivel del hígado y el encéfalo. Recientemente se han desarrollado modelos genéticos de la enfermedad para su estudio clínico. Sin embargo, la utilidad de los mismos es limitada por el hecho de que en tales modelos no se observan manifestaciones neurológicas. El presente estudio tuvo como objetivo desarrollar un modelo de la enfermedad de Wilson en Drosophila melanogaster. Inicialmente se evaluó el efecto de la suplementación con concentraciones de 31 µM y 47 µM de cobre en la sobrevida. Posteriormente se realizaron estudios de conducta para determinar si existían alteraciones en el desempeño motor asociadas al tratamiento con la dosis de 47 µM de cobre. Los resultados obtenidos sugieren que el tratamiento con cobre disminuye la viabilidad de la Drosophila. La disminución de la sobrevida estuvo asociada a un aumento y una disminución de los registros de actividad motora en las etapas tempranas y tardías de la intoxicación respectivamente. Por último, se evaluó el papel del sistema de neurotransmisión dopaminérgico sobre las alteraciones conductuales inducidas por el cobre. El tratamiento con el precursor de la dopamina, L-dopa, indujo un aumento de la actividad motora similar al inducido por el cobre. Por el contrario, el tratamiento con Flufenazina, un antagonista de los receptores dopaminérgicos D2, fue capaz de impedir las alteraciones conductuales en todas las edades evaluadas. Estos resultados sugieren que la Drosophila melanogaster podría ser empleada como modelo para el estudio de posibles intervenciones con potencial terapéutico en la enfermedad de Wilson.

Wilson disease is a hereditary disorder caused by mutations of the ATP7B gene, which leads to intoxication with copper as a result of an unbalance of copper homeostasis. The clinical manifestations resulting from this intoxication are related to the affectation of liver and the encephalon in most cases. Several animal models are currently available for the study of the malady. However, in such models no neurological symptoms are observed, which limits their use for the study of pathogenic effects of this disease on the central nervous system. The aim of the present study was to evaluate if copper feeding could induce a disease state in Drosophila melanogaster to model Wilson disease. The effect of the feeding of copper at the doses of 31 µM and 47 µM on the survival was initially evaluated. Next, behavioral experiments were conducted to determine whether the motor performance was altered by the 47 µM concentration. The results suggest that copper treatment decreases the viability of the flies. In addition, the decrease of viability was associated to an increase and decrease of spontaneous motor activity at early and late stages of the intoxication, respectively. Finally, the role of the dopaminergic neurotransmission system on the observed motor alterations was evaluated. The dopamine precursor L-dopa increased motor activity. In contrast, D2 receptor antagonist, Fluphenazine, was able to block both the increase and decrease of motor activity scores induced by copper. These results suggest that Drosophila melanogaster could be used as a model organism for the study of possible interventions with potential neuroprotective effects in Wilson disease.

The Neuroimmunology of Schizophrenia

Schizophrenia (SCZ) is a polygenic, multi-factorial disorder and a definitive understanding of its pathophysiology has been lacking since it was first described more than a century ago. The predominant pharmacological approach used to treat SCZ is the use of dopamine receptor antagonists. The fact that many patients remain symptomatic, despite complying with medication regimens, emphasises the need for a more encompassing explanation for both the causes and treatment of SCZ. Recent neuroanatomical, neurobiological, environmental and genetic studies have revived the idea that inflammatory pathways are involved in the pathogenesis of SCZ. These new insights have emerged from multiple lines of evidence, including the levels of inflammatory proteins in the central nervous system of patients with SCZ and animal models. This review focuses on aberrant inflammatory mechanisms present both before and during the onset of the psychotic symptoms that characterise SCZ and discusses recent research into adjunctive immune system modulating therapies for its more effective treatment.

Optimal Duration of Medical Treatment in Superior Mesenteric Artery Syndrome in Children

The aim of this study was to investigate the outcome, and optimal duration of medical treatment in children with superior mesenteric artery syndrome (SMAS). Eighteen children with SMAS were retrospectively studied. The data reviewed included demographics, presenting symptoms, co-morbid conditions, clinical courses, nutritional status, treatments, and outcomes. The three most common symptoms were postprandial discomfort (67.7%), abdominal pain (61.1%), and early satiety (50%). The median duration of symptoms before diagnosis was 68 days. The most common co-morbid condition was weight loss (50%), followed by growth spurt (22.2%) and bile reflux gastropathy (16.7%). Body mass index (BMI) was normal in 72.2% of the patients. Medical management was successful in 13 patients (72.2%). The median duration of treatment was 45 days. Nine patients (50%) had good outcomes without recurrence, 5 patients (27.8%) had moderate outcomes, and 4 patients (22.2%) had poor outcomes. A time limit of >6 weeks for the duration of medical management tended to be associated with worse outcomes (P=0.018). SMAS often developed in patients with normal BMI or no weight loss. Medical treatment has a high success rate, and children with SMAS should be treated medically for at least 6 weeks before surgical treatment is considered.

Effects of prokinetic drugs on the abdominal wall wound healing of rats submitted to segmental colectomy and colonic anastomosis / Efeitos de drogas procinéticas na cicatrização da parede abdominal de ratos submetidos à colectomia segmentar e anastomose no cólon esquerdo

PURPOSE: To assess the effect of prokinetic agents on abdominal wall wound healing in rats submitted to segmental colectomy and colonic anastomosis. METHODS: Sixty rats were randomly allocated into three groups according to the agents they would receive in the postoperative period: M (metoclopramide); B (bromopride); and C (control, saline 0.9%). Surgical procedures were performed identically in all animals, and consisted of a midline laparotomy followed by resection of a 1-cm segment of large bowel with end-to-end anastomosis. The abdominal wall was closed in two layers with running stitches. Abdominal wall samples were collected on the 3rd or 7th postoperative day for measurement of breaking (tensile) strength and histopathological assessment. RESULTS: There were no statistically significant differences in tensile strength of the abdominal wall scar between groups M, B, and C, nor between the three and seven days after surgery subgroups. On histopathological assessment, there were no statistically significant between-group differences in collagen deposition or number of fibroblasts at the wound site CONCLUSION: Use of the prokinetic drugs metoclopramide or bromopride had no effect on abdominal wall healing in rats submitted to segmental colectomy and colonic anastomosis.

OBJETIVO: Avaliar os efeitos do uso de drogas prócinéticas na cicatrização da parede abdominal de ratos submetidos à colectomia segmentar e anastomose no cólon esquerdo. MÉTODOS: Foram utilizados 60 ratos, alocados aleatoriamente em três grupos para receberem as seguintes medicações no período pós-operatório: M (metoclopramida); B (bromoprida) e C (solução salina a 0,9%). Os procedimentos cirúrgicos foram idênticos em todos os animais. Foi realizada laparotomia mediana, seguida de colectomia segmentar de 1-cm e anastomose colônica. O fechamento da parede abdominal foi feito em dois planos de sutura contínua. No 3° ou no 7° dia pós-operatório foram coletadas amostras da parede abdominal para medida da força de ruptura e avaliação histopatológica. RESULTADOS: Não houve diferença significativa entre os grupos no que diz respeito à força de ruptura da parede abdominal, nem entre os subgrupos no 3º e 7º dia após a cirurgia. À análise histopatológica não houve alterações na deposição de colágeno ou na quantidade de fibroblastos no sítio da cicatriz. CONCLUSÃO: O uso de drogas prócinéticas, metoclopramida ou de bromoprida, não interferiu na cicatrização da parede abdominal de ratos submetidos à colectomia segmentar e anastomose no cólon esquerdo.

Does metoclopramide impair anastomotic healing of the left colon of rats? / A metoclopramida prejudica a cicatrização de anastomoses do cólon esquerdo de ratos?

PURPOSE: To evaluate the effects of metoclopramide on the formation of adhesion and the healing of left colonic anastomoses in rats. METHODS: Forty rats underwent sectioning of the left colon and end-to-end anastomosis and were divided into two groups of 20 animals for the administration of metoclopramide (experimental group - E) or saline solution (control group - C). Each group was divided into subgroups of 10 animals each to be killed on the third (E3 and C3) or seventh postoperative day (E7 and C7). Adhesion was assessed, and a colonic segment containing the anastomosis was removed for analysis of breaking strength and hydroxyproline concentration. RESULTS: There were no deaths or dehiscence on the 3rd postoperative day. There was one death and one blocked anastomotic dehiscence in the E7 group. No significant differences between groups were found in the analysis of clinical outcome, intra-cavity adhesion, adhesion to the anastomosis or breaking strength on the 3rd and 7th postoperative day. Hydroxyproline concentration was higher in the control group on the 3rd (p=0.006) but not on the 7th postoperative day (p=0.241). CONCLUSION: Metoclopramide did not have harmful effects on the healing of intestinal anastomoses in rats.

OBJETIVO: Avaliar os efeitos da metoclopramida sobre a formação de aderências e a cicatrização de anastomoses de cólon esquerdo de ratos. MÉTODOS: 40 ratos distribuídos em dois grupos contendo 20 animais, para administração de metoclopramida (grupo experimental - E) ou solução de NaCl 0,9 por cento (grupo controle - C). Cada grupo foi dividido em subgrupos contendo 10 animais, para eutanásia no terceiro (E3 e C3) ou sétimo dia (E7 e C7) de pós-operatório. Os ratos foram submetidos à secção do cólon esquerdo e anastomose término-terminal. No dia da re-laparotomia foi avaliada a quantidade total de aderências e removido um segmento colônico contendo a anastomose para análise da força de ruptura e concentração de hidroxiprolina. RESULTADOS: Não houve mortes ou deiscências no 3º dia de pós-operatório. No grupo E7 ocorreram uma morte e uma deiscência de anastomose bloqueada. Não houve diferença significativa entre os grupos em relação à evolução clínica, quantidade de aderências intra-cavitárias ou à anastomose e resistência tênsil no 3º ou 7º pós-operatório. A concentração de hidroxiprolina foi maior no grupo metoclopramida no 3º (p=0,006) mas não no 7º dia de pós-operatório (p=0,241) CONCLUSÃO: A metoclopramida não apresenta efeito deletério sobre a cicatrização de anastomoses intestinais em ratos.

Analgesic Mechanism of Electroacupuncture in an Arthritic Pain Model of Rats: A Neurotransmitter Study

PURPOSE: We investigated what kinds of neurotransmitters are related with electroacupuncture (EA) analgesia in an arthritic pain model of rats. MATERIALS AND METHODS: One hundred rats were assigned to six groups: control, EA, opioid, adrenergic, serotonin and dopamine group. A standardized model of inflammatory arthritis was produced by injecting 2% carrageenan into the knee joint cavity. EA was applied to an acupoint for 30 min in all groups except fo the control group. In the opioid, adrenergic, serotonin and dopamine groups, each receptor antagonist was injected intraperitoneally to their respective group before initiating EA. RESULTS: In the opioid receptor antagonist group, adrenergic receptor antagonist group, serotonin receptor antagonist group, dopamine receptor antagonist group and the control group weight-bearing force decreased significantly from 30 min to 180 min after EA in comparison with the EA group. CONCLUSION: The analgesic effects of EA are related to opioid, adrenergic, serotonin and dopamine receptors in an arthritic pain model of rats.

Parkinson disease drug screening based on the interaction between D(2) dopamine receptor and beta-arrestin 2 detected by capillary zone electrophoresis

Parkinson's disease is the second most common neurodegenerative disease in the world. Beta-arrestin-2 has been reported to be an important protein involved in D(2) dopamine receptor desensitization, which is essential to Parkinson's disease. Moreover, the potential value of pharmacological inactivation of G protein-coupled receptor kinase or arrestin in the treatment of patients with Parkinson's disease has recently been shown. We studied the interaction between D(2) dopamine receptor and beta-arrestin-2 and the pharmacological regulation of chemical compounds on such interaction using capillary zone electrophoresis. The results from screening more than 40 compounds revealed three compounds that remarkably inhibit the beta-arrestin-2/D(2) dopamine receptor interaction among them. These compounds are promising therapies for Parkinson's disease, and the method used in this study has great potential for application in large-scale drug screening and evaluation.

Formulation and in vitro characterization of domperidone loaded solid lipid nanoparticles and nanostructured lipid carriers

Domperidone [DOM] is a dopamine-receptor [D[2]] antagonist, widely used in the treatment of motion-sickness. The pharmacokinetic parameters of DOM make it a suitable candidate for development of Solid Lipid Nanoparticle [SLN] and Nanostructured Lipide Carrier [NLC]. The purpose of the present investigation was to prepare and evaluate DOM loaded solid lipid nanoparticles [DOM-SLN] and DOM loaded nanostructured lipid carriers [DOM-NLC]. DOM loaded SLN and NLC were prepared by hot homogenization followed by ultrasonication technique, using trimyristin as solid lipid, cetyl recinoleate as liquid lipid and a mixture of soy phosphatidylcholine [99%] and tween 80 as surfactant. SLN and NLC were characterized for particle size, polydispersity index [PDI], zeta potential and entrapment efficiency. The effects of composition of lipid materials and surfactant mixture on the particle size, PDI, zeta potential, drug entrapment efficiency, and in vitro drug release behavior were investigated. DSC analysis was performed to characterize the state of drug and lipid modification. Shape and surface morphology were determined by transmission electron microscopy [TEM]. SLN and NLC formulations were subjected to stability study over a period of 40 days. The mean particle size, PDI, zeta potential and entrapment efficiency of optimized SLN [SLN1] and NLC were found to be 30.45 nm, 0.156, 12.40 mV, 87.84% and 32.23 nm, 0.160, 10.47 mV, 90.49% respectively. DSC studies revealed that DOM was in an amorphous state and triglycerides were in the beta prime form in SLN and NLC. Shape and surface morphology was determined by TEM revealed fairly spherical shape of nanoparticles. In vitro release studies demonstrated that both the SLN and NLC formulations possessed a controlled release over a period of 24 hrs. SLN and NLC formulations were subjected to stability over a period of 40 days. There was no significant [P < 0.05] change in particle size, zeta potential, PDI and entrapment efficiency indicating the developed SLN and NLC were fairly stable. Fairly spherical shaped, stable and controlled release DOM-SLN and DOM-NLC could be prepared by hot homogenization followed by ultrasonication technique

Influence of metoclopramide on abdominal wall healing in rats subjected to colonic anastomosis in the presence of peritoneal sepsis induced / Influência da metoclopramida na cicatrização da parede abdominal de ratos submetidos à anastomose colônica na vigência de sepse peritonial induzida

PURPOSE: To evaluate the effects of metoclopramide on abdominal wall healing in rats in the presence of sepsis. METHODS: 40 rats divided into two groups of twenty animals, subdivided into two subgroups of 10 animals each: group (E) - treated with metoclopramide, and saline-treated control group. The two groups were divided into subgroups of 10 to be killed on the 3rd day (n = 10) or day 7 (n = 10) after surgery. Sepsis was induced by cecal ligation and puncture. We performed also the section and anastomosis in left colon. The synthesis of the abdominal wall was made with 3-0 silk thread. We measured the breaking strength of the abdominal wall and made the histopathological evaluation. RESULTS: on 3rd day postoperative, the average breaking strength in the E group was 0.83 ± 0.66 and in group C was 0.35 ± 0.46 (p = 0.010). On the seventh day, the breaking strength in group E was11.44 ± 5.07, in group C 11.66 ± 7.38 (p = 1.000). The E7 group showed lower inflammatory infiltration, foreign body reaction, fibrin than control. CONCLUSION: animals treated with metoclopramide had a higher resistance of the abdominal wall on the 3rd postoperative day.

OBJETIVO: Avaliar os efeitos da metoclopramide na cicatrização da parede abdominal de ratos na vigência de sepse. METHODS: 40 ratos divididos em dois grupos de 20 animais, subdivididos em dois subgrupos de 10 animais cada: grupo (E) - tratado com metoclopramida, e o grupo controle tratado com solução fisiologica. Os dois grupos foram divididos em subgrupos de de 10 para serem mortos no dia 3 (n = 10) ou o dia 7 (n = 10) após a cirurgia. A sepse foi induzida por ligadura e perfuração cecal. Foi realizada também a secção e anastomose em cólon esquerdo. A síntese da parede abdominal foi feita com fio de seda 3-0. Mediu-se a força de ruptura da parede abdominal e foi feita uma avaliação histopatológica. RESULTADOS: No dia 3 pós-operatório, a força média de ruptura no grupo E foi de 0,83 ± 0,66 e no grupo C foi de 0,35 ± 0,46 (p = 0,010). No sétimo dia, a força de ruptura no grupo E foi 11.44 ± 5,07; no grupo C, 11,66 ± 7,38 (p = 1,000). O grupo E7 apresentou menor infiltração inflamatória e reação de corpo estranho do que o controle de fibrina. CONCLUSÃO: Animais tratados com metoclopramida apresentaram uma maior resistência da parede abdominal no 3º dia pós-operatório.

Hiperprolactinemia / Hyperprolactinemia

A hiperprolactinamia é a alteração hormonal mais comum do eixo hipotalâmico-hipofisário encontrada na prática clinica Apresenta predomínio na população feminina e está associada com a galactorréia, distúrbios mentruais, infertilidade, hipogonadismo e diminuição da libido. As causas são numerosas, sendo o uso de fármacos a causa geral mais comum, e os prolactinomas a causa patológica mais frequente. Atualmente o tratamento farmacológico com agonistas dopaminérgicos tem se apresentado como primeira opção no tratamento, ficando a cirurgia e a radioterapia indicadas a casos reservados. O presente artigo versará sobre os aspectos etilógicos, as manifestações clinicas, investigação diagnóstica e opções de tratamento de hiperprolactinemia.