Seroprevalence of Trypanosoma cruzi in kidney transplant donors and recipients in Mexico City.

Infectious diseases are common causes of morbidity and mortality among kidney transplant recipients. Chagas disease (CD) has been recognized as an emerging infectious complication of transplantation caused by the parasite Trypanosoma cruzi. CD is prevalent in Mexico, particularly in the southern coastal region. The impact on Mexican kidney transplant programs has not been previously studied prospectively. From 2009 through 2010, serum samples from 59 kidney transplant donors and 405 renal transplant recipients were screened for antibodies against T. cruzi. Serum was initially screened using a locally developed ELISA test; positive results were confirmed by an indirect immunofluorescense test, in accordance with Panamerican Health Organization/World Health Organization guidelines. None of the donors were seropositive for T. cruzi, while 8 (1.97%) kidney transplant recipients were confirmed to be seropositive for T. cruzi. None of them have developed clinical manifestations of CD, although specific screening of recipients was not performed. A prospective study is planned to define the epidemiology and outcome of CD among kidney transplant donors and recipients in Mexico more thoroughly.

Immune response after rabies vaccine in a kidney transplant recipient.

A 48-year-old male kidney-transplant recipient was bitten by a rabid dog. His immunosuppressive treatment consisted of cyclosporine 60 mg b.i.d., mycophenolate mofetil (MMF) 250 mg t.i.d., and prednisone 5 mg. After wound care, he received 5 doses of purified vero cell rabies vaccine on days 0, 3, 7, 14, and 28, and human rabies immunoglobulin, according to international guidelines. Adequate levels of rabies virus neutralizing antibodies were observed after the administration of the third vaccine dose. However, a decrease of antibody titer was detected by day 28. Immunosuppressive medication was minimized, withdrawing MMF and reducing the dose of cyclosporine. Booster doses of the same vaccine were administered on days 38, 41, 45, 52, and 66. Adequate neutralizing antibody response was recovered during the ensuing 12 months, under reduced immunosuppression. Nineteen months after the incident, the patient remains with good graft function and is asymptomatic for rabies. It remains to be determined whether the attained immune response was either the result of the booster vaccinations or the reduction of immunosuppression alone. Nevertheless, such an outcome would have been possible only with the combined management strategy implemented.

[Preoperative concentration of plasma fibrinogen as a predictor of bleeding in total hip arthroplasty]. / Concentración preoperatoria de fibrinógeno plasmático como predictor de sangrado en artroplastía total de cadera.

INTRODUCTION: Total hip arthroplasty is popular for its success in treating coxarthrosis, its associated with substantial blood loss. Significant bleeding causes complications such as increase in hospitalization days, higher costs, exposing the patient to complications associated with blood transfusion. The aim of the study is to investigate the association between preoperative plasma fibrinogen concentration and trans-surgical bleeding and determine fibrinogen level cut-off to present greater trans-surgical bleeding. MATERIAL AND METHODS: Retrospective, observational, analytical study, from June to December 2020, including 227 patients with Kellgren and Lawrence scale IV coxarthrosis undergoing primary total hip arthroplasty, beneficiaries, older than 18 years, without liver or hematological diseases, and history of significant surgical bleeding. RESULTS: Mean preoperative hemoglobin value was 14.6 ± 1.3 g/dl, after surgery (48 hours) 10.5 ± 1.4 g/dl; decrease of 4.1 ± 1.2 g/dl (p 0.0001). Mean preoperative hematocrit value 43% [41-45], after the procedure; 32% [29-35]; decrease of 11% [8-14] (p 0.0001). 98 patients had intraoperative bleeding 300 ml, 129 had 300 ml; 61.2% of patients with bleeding greater than 300 ml had fibrinogen values below the cut-off point (388 mg/dl). CONCLUSION: In postoperative patients, preoperative fibrinogen levels 388 mg/dl and age 58 years were associated with an increased risk of OR = 0.18 (95% CI 0.10-0.32) of presenting trans-surgical bleeding 300 ml, with a decrease in Hb of 4.1 ± 1.2 g/dl (p = 0.0001) and Hto of 11% [8-14] (p = 0.0001) between the pre and postoperative period in 48 hours.

INTRODUCCIÓN: La artroplastía total de cadera tiene popularidad debido al éxito en el tratamiento de coxartrosis; son procedimientos asociados a la pérdida de sangre. Un sangrado importante provoca complicaciones como aumento en días de estancia intrahospitalaria, mayor costo de la enfermedad, exponiendo al paciente a complicaciones asociadas a transfusión sanguínea. El objetivo del estudio es investigar asociación entre concentración de fibrinógeno plasmático preoperatorio con sagrado transquirúrgico y determinar el nivel de corte de fibrinógeno para presentar mayor sangrado transquirúrgico. MATERIAL Y MÉTODOS: Estudio retrospectivo, observacional, analítico, de Junio a Diciembre de 2020, incluyendo 227 pacientes con coxartrosis IV de la escala de Kellgren y Lawrence sometidos a artroplastía total primaria de cadera, derechohabientes, mayores de 18 años, en ausencia de enfermedades hepáticas o hematológicas y antecedente de sangrado quirúrgico importante. RESULTADOS: El valor promedio de hemoglobina preoperatoria fue 14.6 ± 1.3 g/dl, posterior a cirugía (48 horas) 10.5 ± 1.4 g/dl; observando descenso de 4.1 ± 1.2 g/dl (p 0.0001). Valor promedio del hematocrito prequirúrgico 43% [41-45], posterior al procedimiento 32% [29-35]; se observó descenso de 11% [8-14] (p 0.0001); 98 pacientes presentaron sangrado transquirúrgico 300 ml; 129 tuvieron sangrado 300 ml; 61.2% de pacientes con sangrado mayor de 300 ml mostraron valores de fibrinógeno debajo del punto de corte (388 mg/dl). CONCLUSIÓN: En pacientes postoperados los niveles preoperatorios de fibrinógeno 388 mg/dl y edad 58 años se asociaron al aumento en el riesgo del OR = 0.18 (IC 95% 0.10-0.32) de presentar sangrado transquirúrgico 300 ml, con descenso de la Hb de 4.1 ± 1.2 g/dl (p = 0.0001) y Hto de 11% [8-14] (p = 0.0001) entre el preoperatorio y el postoperatorio en 48 horas.

[Joint hypermobility syndrome]. / Síndrome de hipermovilidad articular.

Joint hypermobility syndrome is an inherited disorder with autosomal dominant pattern; is characterized by joint hyperlaxity and musculoskeletal pains. Thermal hypermobility refers to the increase in active or passive movements of joints based on their normal ranges. Joint hypermobility syndrome also has gastrointestinal symptoms, sleep disorders, fibromyalgia, psychological disorders, migraine headache, ophthalmic, autonomic, among others. To diagnose hypermobility syndrome, Brighton's criteria are generally accepted and published in 1998. This criteria also known as benign joint hypermobility syndrome. The term benign is used to distinguish it from other more severe conditions such as Ehler-Danlos (classic or vascular type), Marfan syndrome, and imperfect osteogenesis. Treatment with physiotherapy and pharmacological means help improve patients' quality of life.

El síndrome de hipermovilidad articular es un desorden hereditario con patrón autosómico dominante; se caracteriza por hiperlaxitud articular y dolores musculoesqueléticos. El término hipermovilidad se refiere al incremento en los movimientos activos o pasivos de las articulaciones con base en sus rangos normales. El síndrome de hipermovilidad articular presenta además síntomas gastrointestinales, trastornos de sueño, fibromialgia, trastornos sicológicos, cefalea migrañosa, oftálmicos, autonómicos, entre otros. Para diagnosticar el síndrome de hipermovilidad, en general son aceptados los criterios de Brighton, los cuales fueron publicados en 1998. También se le conoce como síndrome de hipermovilidad articular benigno. El término benigno se utiliza para distinguirlo de otras condiciones más severas como Ehler-Danlos (tipo clásico o vascular), síndrome de Marfan y osteogénesis imperfecta. El tratamiento con fisioterapia y medidas farmacológicas ayudan a mejorar la calidad de vida de los pacientes.

Severe alterations in expression and localisation of {alpha}6{beta}4 integrin in salivary gland acini from patients with Sjogren syndrome.

OBJECTIVES: In salivary glands from patients with Sjögren syndrome, overexpression of laminins 1 and 5 and disorganisation of the acinar basal lamina have been reported. Laminin 5 mediates association of the basal lamina with epithelial cells by forming adhesion complexes upon interaction with alpha6beta4 integrin. In the present work, mRNA and protein levels of alpha6beta4 integrin were determined and its localisation in salivary glands evaluated in patients with Sjögren syndrome. METHODS: Salivary glands of 12 patients with Sjögren syndrome and 8 controls were studied. The mRNA and protein levels of alpha6beta4 were determined by semiquantitative reverse transcriptase (RT)-PCR and western blot analysis, respectively. The subcellular localisation of alpha6beta4 and laminin were evaluated by confocal microscopy. RESULTS: In patients, no significant differences in alpha6 and beta4 mRNA levels were detected. However, beta4 integrin protein levels were significantly lower, whereas, changes in alpha6, were highly variable. In controls, alpha6beta4 was detected in the basolateral and basal surface of serous and mucous acini, respectively. In patients, alterations in alpha6beta4 distribution were particularly dramatic for acini with strong basal lamina disorganisation. alpha6beta4 was also detected in the cytoplasm and lateral plasma membrane in serous and mucous acini. CONCLUSION: Mild alterations in the basal lamina correlated with lateral redistribution of alpha6beta4 integrin and the formation of new cell-cell adhesions that help maintain acinar organisation and promote cell survival. Conversely, in cases with severe basal lamina alterations, lateral alpha6beta4 redistribution was no longer sufficient to maintain acinar cell survival. Thus, maintenance of equilibrium between cell-cell and cell-basal lamina attachment is required to sustain gland cell survival.

Tactile shape processing.

Neuroimaging techniques may aid in the identification of areas of the human brain that are involved in tactile shape perception. Bodegård et al. (2001) relate differences in the properties of tactile stimuli to differences in areas of cortical activation to infer tactile processing in the somatosensory network.

Sensing without touching: psychophysical performance based on cortical microstimulation.

Unequivocal proof that the activity of a localized cortical neuronal population provides sufficient basis for a specific cognitive function has rarely been obtained. We looked for such proof in monkeys trained to discriminate between two mechanical flutter stimuli applied sequentially to the fingertips. Microelectrodes were inserted into clusters of quickly adapting (QA) neurons of the primary somatosensory cortex (S1), and the first or both stimuli were then substituted with trains of current pulses during the discrimination task. Psychophysical performance with artificial stimulus frequencies was almost identical to that measured with the natural stimulus frequencies. Our results indicate that microstimulation can be used to elicit a memorizable and discriminable analog range of percepts, and shows that activation of the QA circuit of S1 is sufficient to initiate all subsequent neural processes associated with flutter discrimination.

Reduced sulfation of muc5b is linked to xerostomia in patients with Sjögren syndrome.

OBJECTIVES: MUC5B contains sulfated and sialylated oligosaccharides that sequester water required for moisturising the oral mucosa. Xerostomia, in patients with Sjögren syndrome, is generally associated with reduced quantities, rather than altered properties, of saliva. Here, we determined the amount of MUC5B (mRNA and protein) as well as sulfation levels in salivary glands of patients with normal or altered unstimulated salivary flow. Localisation of MUC5B and sulfated MUC5B, as well as total levels sulfated groups were determined and compared with acini basal lamina disorganisation. PATIENTS AND METHODS: In all, 18 patients with normal or altered unstimulated salivary flow and 16 controls were studied. MUC5B mRNA and protein were evaluated in salivary glands by semiquantitative RT-PCR and Western blot analysis. MUC5B sulfation was determined by Western blotting. MUC5B and sulfo-Lewis(a) antigen localisation were assessed by immunohistochemistry. The total amount of sulfated oligosaccharides was determined microdensitometrically. RESULTS: No significant differences were detected in MUC5B mRNA and protein levels between controls and patients, while sulfo-Lewis(a) antigen levels were lower in patients. The number of sulfo-Lewis(a) positive mucous acini was reduced in patients but no correlation was observed between lower levels of sulfation and unstimulated salivary flow. Microdensitometric data confirmed the presence of reduced sulfated oligosaccharides levels in mucous acini from patients with highly disorganised basal lamina. CONCLUSION: Disorganisation of the basal lamina observed in patients with Sjögren syndrome may lead to dedifferentiation of acinar mucous cells and, as a consequence, alter sulfation of MUC5B. These changes are suggested to represent a novel mechanism that may explain xerostomia in these patients.

Sensing and deciding in the somatosensory system.

Combined psychophysical and neurophysiological experiments have revealed some of the neural codes associated with perception and processing of tactile information. Recently, intracortical microstimulation was used to demonstrate a causal link between primary cortical activity and perception. Evidence for a subsequent link, between a sensory decision process and its expression as a movement, has been found in motor areas.

Concentración preoperatoria de fibrinógeno plasmático como predictor de sangrado en artroplastía total de cadera / Preoperative concentration of plasma fibrinogen as a predictor of bleeding in total hip arthroplasty

Resumen: Introducción: La artroplastía total de cadera tiene popularidad debido al éxito en el tratamiento de coxartrosis; son procedimientos asociados a la pérdida de sangre. Un sangrado importante provoca complicaciones como aumento en días de estancia intrahospitalaria, mayor costo de la enfermedad, exponiendo al paciente a complicaciones asociadas a transfusión sanguínea. El objetivo del estudio es investigar asociación entre concentración de fibrinógeno plasmático preoperatorio con sagrado transquirúrgico y determinar el nivel de corte de fibrinógeno para presentar mayor sangrado transquirúrgico. Material y métodos: Estudio retrospectivo, observacional, analítico, de Junio a Diciembre de 2020, incluyendo 227 pacientes con coxartrosis IV de la escala de Kellgren y Lawrence sometidos a artroplastía total primaria de cadera, derechohabientes, mayores de 18 años, en ausencia de enfermedades hepáticas o hematológicas y antecedente de sangrado quirúrgico importante. Resultados: El valor promedio de hemoglobina preoperatoria fue 14.6 ± 1.3 g/dl, posterior a cirugía (48 horas) 10.5 ± 1.4 g/dl; observando descenso de 4.1 ± 1.2 g/dl (p ≤ 0.0001). Valor promedio del hematocrito prequirúrgico 43% [41-45], posterior al procedimiento 32% [29-35]; se observó descenso de 11% [8-14] (p ≤ 0.0001); 98 pacientes presentaron sangrado transquirúrgico ≥ 300 ml; 129 tuvieron sangrado ≤ 300 ml; 61.2% de pacientes con sangrado mayor de 300 ml mostraron valores de fibrinógeno debajo del punto de corte (388 mg/dl). Conclusión: En pacientes postoperados los niveles preoperatorios de fibrinógeno ≤ 388 mg/dl y edad ≥ 58 años se asociaron al aumento en el riesgo del OR = 0.18 (IC 95% 0.10-0.32) de presentar sangrado transquirúrgico ≥ 300 ml, con descenso de la Hb de 4.1 ± 1.2 g/dl (p = 0.0001) y Hto de 11% [8-14] (p = 0.0001) entre el preoperatorio y el postoperatorio en 48 horas.

Abstract: Introduction: Total hip arthroplasty is popular for its success in treating coxarthrosis, its associated with substantial blood loss. Significant bleeding causes complications such as increase in hospitalization days, higher costs, exposing the patient to complications associated with blood transfusion. The aim of the study is to investigate the association between preoperative plasma fibrinogen concentration and trans-surgical bleeding and determine fibrinogen level cut-off to present greater trans-surgical bleeding. Material and methods: Retrospective, observational, analytical study, from June to December 2020, including 227 patients with Kellgren and Lawrence scale IV coxarthrosis undergoing primary total hip arthroplasty, beneficiaries, older than 18 years, without liver or hematological diseases, and history of significant surgical bleeding. Results: Mean preoperative hemoglobin value was 14.6 ± 1.3 g/dl, after surgery (48 hours) 10.5 ± 1.4 g/dl; decrease of 4.1 ± 1.2 g/dl (p ≤ 0.0001). Mean preoperative hematocrit value 43% [41-45], after the procedure; 32% [29-35]; decrease of 11% [8-14] (p ≤ 0.0001). 98 patients had intraoperative bleeding ≥ 300 ml, 129 had ≤ 300 ml; 61.2% of patients with bleeding greater than 300 ml had fibrinogen values below the cut-off point (388 mg/dl). Conclusion: In postoperative patients, preoperative fibrinogen levels ≤ 388 mg/dl and age ≥ 58 years were associated with an increased risk of OR = 0.18 (95% CI 0.10-0.32) of presenting trans-surgical bleeding ≥ 300 ml, with a decrease in Hb of 4.1 ± 1.2 g/dl (p = 0.0001) and Hto of 11% [8-14] (p = 0.0001) between the pre and postoperative period in 48 hours.

Síndrome de hipermovilidad articular / Joint hypermobility syndrome

Resumen: El síndrome de hipermovilidad articular es un desorden hereditario con patrón autosómico dominante; se caracteriza por hiperlaxitud articular y dolores musculoesqueléticos. El término hipermovilidad se refiere al incremento en los movimientos activos o pasivos de las articulaciones con base en sus rangos normales. El síndrome de hipermovilidad articular presenta además síntomas gastrointestinales, trastornos de sueño, fibromialgia, trastornos sicológicos, cefalea migrañosa, oftálmicos, autonómicos, entre otros. Para diagnosticar el síndrome de hipermovilidad, en general son aceptados los criterios de Brighton, los cuales fueron publicados en 1998. También se le conoce como síndrome de hipermovilidad articular benigno. El término benigno se utiliza para distinguirlo de otras condiciones más severas como Ehler-Danlos (tipo clásico o vascular), síndrome de Marfan y osteogénesis imperfecta. El tratamiento con fisioterapia y medidas farmacológicas ayudan a mejorar la calidad de vida de los pacientes.

Abstract: Joint hypermobility syndrome is an inherited disorder with autosomal dominant pattern; is characterized by joint hyperlaxity and musculoskeletal pains. Thermal hypermobility refers to the increase in active or passive movements of joints based on their normal ranges. Joint hypermobility syndrome also has gastrointestinal symptoms, sleep disorders, fibromyalgia, psychological disorders, migraine headache, ophthalmic, autonomic, among others. To diagnose hypermobility syndrome, Brighton's criteria are generally accepted and published in 1998. This criteria also known as benign joint hypermobility syndrome. The term benign is used to distinguish it from other more severe conditions such as Ehler-Danlos (classic or vascular type), Marfan syndrome, and imperfect osteogenesis. Treatment with physiotherapy and pharmacological means help improve patients' quality of life.

Uso de perifiton en un sistema de policultivo en agro acuicultura integrada en la comunidad indígena de Jimaín, Sierra Nevada de Santa Marta (Colombia) / Periphyton-based polyculture in an integrated agri-aquaculture system at the indigenous community of Jimaín, Sierra Nevada de Santa Marta (Colombia)

RESUMEN Los Sistemas de Agro Acuicultura Integrada (SAAI) han sido estudiados como opción para la producción de pescado en comunidades con recursos limitados. Así mismo, el uso de perifiton se ha convertido recientemente en una alternativa viable por el aporte de alimento natural de bajo costo. El objetivo de este estudio fue evaluar el efecto del perifiton sobre el desempeño productivo del policultivo Piaractus sp. (cachama híbrida) y Prochilodus magdalenae (bocachico) en SAAI en la comunidad Indígena de Jimaín, Colombia. Se sembraron 1,5 alevinos de cachama híbrida y 1,5 bocachicos/m2, con peso promedio de 0,49 ± 0,14 g y 1,83 ±1,61 g respectivamente, en seis estaques en tierra de 90 m2 tres de los cuales contaron con varas de madera (3 varas/m2) para la fijación de perifiton. La duración del cultivo fue de 135 días. Los tratamientos (CS: con sustrato y SS: sin sustratos) recibieron una dieta suplementaria dos veces al día, calculada como porcentaje de la biomasa con ajuste quincenal. Se realizaron biometrías quincenales. Los datos productivos por especie y para el policultivo se evaluaron mediante ANOVA con un modelo lineal general (p < 0,05). Los datos de peso (g) y longitud estándar (cm) por especie se evaluaron mediante un modelo mixto de medidas repetidas. No se encontraron efectos del sustrato sobre los parámetros productivos analizados tanto para cada especie, como para el policultivo. Se presentó interacción significativa para el peso del bocachico el día 90 (CS: 74,7 y SS: 47,1). Según los resultados obtenidos, la utilización de perifiton y el manejo en policultivo de especies nativas requiere más estudios.

ABSTRACT Integrated agri-aquaculture systems (IAAS) have been studied as an option for fish production in communities with limited resources. Likewise, the use of periphyton has recently become a viable alternative for its contribution of low-cost natural food. The effect of periphyton use on the productive yield of a hybrid cachama and bocachico polyculture in IAAS, was studied in the Jimaín Indigenous community, Colombia. For this experiment, 1.5 hybrid cachama and 1.5 bocachico fingerlings/m2 were stocked with average weights of 0.49 ± 0.14 g and 1.83 ± 1.61 g, respectively, in six 90 m2 land ponds; three of these ponds had wooden dowels (three dowels/m2) for periphyton fixation. The growth evaluation lasted 135 days. The treatments (WS: with substrate and WOS: without substrates) received a supplementary diet, adjusted as a percentage of the biomass with biweekly adjustment, twice a day. Biometrics were performed every two weeks. The productive data by species and for the polyculture were evaluated using an ANOVA with a general linear model (p <0.05). Weight (g) and standard length (cm) data by species were evaluated using a mixed model of repeated measures. No substrate effects were found on the productive parameters analyzed for each species as well as for the polyculture. A significant interaction was observed for bocachico weight on day 90 (WS: 74.7 and WOS: 47.1). According to the obtained results, optimizing the use of periphyton and the management of native species polyculture requires further studies.

In vivo presynaptic control of dopamine release in the cat caudate nucleus--III. Further evidence for the implication of corticostriatal glutamatergic neurons.

In confirmation of previous results, experiments in halothane-anaesthetized cats implanted with push-pull cannulae showed that the unilateral application of GABA (10(-5) M for 30 min) into the left thalamic motor nuclei (either ventralis medialis, or ventralis lateralis) markedly stimulated the release of [3H]dopamine continuously synthesized from [3H]tyrosine in both caudate nuclei and in the contralateral substantia nigra. Three types of experiments confirmed that the changes in [3H]dopamine release evoked in both caudate nuclei resulted from a presynaptic facilitation mediated by the bilateral corticostriatal glutamatergic projection: The constant delivery of 2-amino 6-trifluoromethoxy benzothiazole (PK 26124) (10(-5) M) to the left caudate nucleus prevented the increased release of [3H]DA evoked by application of gamma-aminobutyric acid (GABA) (10(-5)M) into ventralis medialis-ventralis lateralis while an enhanced release of [3H]dopamine still occurred in the contralateral caudate nucleus. Since PK 26124 is an antagonist of glutamatergic transmission, the presynaptic facilitation may involve glutamatergic neurons. Single unit recordings of dopamine cells in the contralateral substantia nigra indicated that the increased release of [3H]dopamine from dendrites evoked by the application of GABA (10(-5)M) into ventralis medialis-ventralis lateralis was associated with a reduction in the firing rate of dopamine cells. Thus, the enhanced release of [3H]dopamine in the contralateral caudate nucleus may involve a presynaptic facilitatory process. Finally, the unilateral lesion of the sensory motor cortex made prior to the superfusion of caudate nucleus with [3H]tyrosine prevented the responses evoked in the two caudate nuclei by the application of GABA (10(-4) M) into ventralis medialis-ventralis lateralis.(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo presynaptic control of dopamine release in the cat caudate nucleus--I. Opposite changes in neuronal activity and release evoked from thalamic motor nuclei.

Halothane-anaesthetized cats implanted with three push-pull cannulae were used to estimate the effects of gamma-aminobutyric acid (GABA) application (either 10(-3) M or 10(-5) M) into the left motor nuclei of the thalamus (either ventralis medialis, or ventralis lateralis) on the firing rate of dopamine cells in the left substantia nigra (caudomedial part) and on the release of [3H]dopamine continuously synthesized from [3H]tyrosine, in the left substantia nigra (caudomedial part) and the left caudate nucleus. Preliminary experiments were performed to establish the electrophysiological characteristics of dopamine cells and non-dopamine cells in the pars compacta (mediocaudal part of substantia nigra) in groups of animals with the electrode inserted within the nigral push-pull cannula or with the electrode inserted in the absence of a push-pull cannula. Dopamine and non-dopamine cells were distinguished according to several criteria (shape of the spike, duration of spike, frequency of discharge, conduction velocity estimated following antidromic activation from the caudate nucleus for dopamine cells or from the ventralis medialis for non-dopamine cells). Data obtained from recordings made within the push-pull cannula were identical to those obtained in the absence of the cannula. In addition both the intravenous injection of amphetamine or its local application (10(-6) M) in the substantia nigra inhibited the firing rate of dopamine cells. When GABA was applied at 10(-3) M for 30 min into the ventralis medialis-ventralis lateralis the multi-unit activity of thalamic cells recorded within the push-pull cannula was inhibited. Single unit activity of dopamine cells was also inhibited and [3H]dopamine release was reduced in the caudate nucleus and increased in the substantia nigra. These results suggest that under these conditions, dopamine release from nerve terminals depended upon nerve activity and that dopamine released from dendrites inhibited the activity of dopamine cells. When GABA was applied at 10(-5) M for 30 min into the ventralis medialis-ventralis lateralis, multi-unit activity of thalamic cells was increased, single-unit activity of dopamine cells was inhibited and [3H]dopamine release was enhanced in the ipsilateral caudate nucleus and not affected in the left substantia nigra, demonstrating that in this situation the release of dopamine from nerve terminals was not dependent on the firing rate of dopamine cells. In addition, these results indicated that the activity of dopamine cells was not always dependent on the dendritic release of dopamine.(ABSTRACT TRUNCATED AT 400 WORDS)

Protection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism by the catecholamine uptake inhibitor nomifensine: behavioral analysis in monkeys with partial striatal dopamine depletions.

The neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on dopamine neurons in monkeys were found to be reduced when the catecholamine uptake inhibitor nomifensine was administered during several weeks after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The obtained protection was partial, leading to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced changes in dopamine levels to 8, 16, 52 and 59% of control values in the caudate nucleus and to 10, 16, 101 and 99% in the putamen of four animals, respectively. At the same doses, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine alone is known to deplete striatal dopamine levels to 0.5-7% of control values. Extra-nigrostriatal monoamine neurons were generally well protected by nomifensine. Neurological examinations revealed modest hypokinesia for a maximum of 10 days after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the two more severely affected animals. Reaction times of arm and eye movements were measured in a formal task in two of the monkeys having a moderate and a more important depletion of striatal dopamine, respectively. Only moderate impairments were seen during the initial 2 weeks after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in both animals. All parameters recovered to control levels thereafter. At 3.5 and 5.5 months after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, task performance was significantly better than control. The speed of arm movement remained largely unaffected during all periods of experimentation. Spontaneous eye movements were reduced in frequency and amplitude during the initial 1-2 weeks after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and recovered completely thereafter. These data suggest a substantial reduction of neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by inhibition of catecholamine uptake. Particularly striking was the absence of major and permanent impairments in behavioral tests in which monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine alone were severely impaired. These results may warrant the development of new catecholamine uptake inhibitors for protecting nigrostriatal dopamine neurons against potential environmental toxins.

In vivo presynaptic control of dopamine release in the cat caudate nucleus--II. Facilitatory or inhibitory influence of L-glutamate.

The local effects of various concentrations of L-glutamate (from 10(-8) M up to 10(-3) M) on the release of [3H]dopamine synthesized continuously from [3H]tyrosine were examined in the caudate nucleus of halothane-anaesthetized cats implanted with push-pull cannulae. When used at a concentration of 10(-8) M or 10(-7) M, L-glutamate stimulated the release of [3H]dopamine from nerve terminals of the nigrostriatal dopamine neurons. This effect was still observed in the presence of tetrodotoxin (5 X 10(-7) M) but it was antagonized by 2-amino 6-trifluoromethoxy benzothiazole (PK 26124) (10(-5) M), an antagonist dopamine nerve terminals. While no significant change in the release of [3H]dopamine was observed with 10(-6) M L-glutamate, higher concentrations (from 10(-5) M to 10(-3) M) of the amino acid produced a long-lasting reduction in the [3H]transmitter release. This latter effect was also antagonized by PK 26124 (10(-5) M) but, unlike that observed with 10(-8) M L-glutamate, it did not persist in the presence of tetrodotoxin (5 X 10(-7) M). On the contrary, a marked stimulation of the release of [3H]dopamine was seen in the presence of this neurotoxin. The reduction in the release of [3H]dopamine produced by 10(-4) M L-glutamate was also antagonized by bicuculline (10(-5) M) and moreover a marked stimulation of [3H]dopamine release took place in the presence of this gamma-aminobutyric acid (GABA) antagonist. Therefore, high concentrations of L-glutamate exerted an inhibitory presynaptic control on [3H]dopamine release which seemed to be indirect and mediated partly by GABAergic neurons. Since a sustained reduction in the spontaneous release of [3H]dopamine was seen in the presence of PK 26124, the corticostriatal glutamatergic neurons appeared to exert a tonic facilitatory presynaptic influence on dopamine release. This effect was important since it represented 40% of the tetrodotoxin-sensitive release of the [3H]transmitter. The direct (stimulatory) and indirect (inhibitory) presynaptic controls on dopamine release mediated by corticostriatal glutamatergic fibres are discussed in light of previous findings and of the anatomical organization of the caudate nucleus.

Effects of unilateral electrical stimulation of various thalamic nuclei on the release of dopamine from dendrites and nerve terminals of neurons of the two nigrostriatal dopaminergic pathways.

The role of several motor and intralaminar thalamic nuclei in the regulation of dopamine release from terminals and dendrites of the nigrostriatal dopaminergic neurons was investigated in halothane-anaesthetized cats. For this purpose, the effects of the unilateral electrical stimulation of various thalamic nuclei on the release of newly synthesized [3H]dopamine were simultaneously determined in both substantiae nigrae and caudate nuclei using the push-pull cannula method. The electrical stimulation of the motor nuclei was the only one to induce asymmetric changes in the four structures since [3H]dopamine release was enhanced in the ipsilateral caudate nucleus and reduced in the contralateral structure while opposite responses were observed in the corresponding substantiae nigrae. A reduction of [3H]dopamine release occurred in the four structures or only in the contralateral substantia nigra and caudate nucleus following the stimulation of the parafascicularis nucleus and the adjacent posterior part of the nucleus centrum medianum or of the nucleus centralis lateralis and the adjacent paralaminar part of the nucleus medialis dorsalis, respectively. The stimulation of the anterior part of the nucleus centrum medianum, which in contrast to other thalamic nuclei examined, receives few nigral inputs, selectively enhanced [3H]dopamine release in the contralateral substantia nigra. No significant changes in [3H]dopamine release were seen either in the substantiae nigrae or in the caudate nuclei following the stimulation of midline thalamic nuclei. These results indicate that the motor and intralaminar thalamic nuclei exert multiple and selective influences on the release of dopamine from terminals and/or dendrites of the dopaminergic neurons. They also further support a role of thalamic nuclei in the transfer of information from one substantia nigra to the contralateral dopaminergic neurons. The possible involvement of connections between paired thalamic nuclei was underlined by the observations of evoked potentials in contralateral homologous nuclei following unilateral stimulation of motor, or some intralaminar, nuclei. The present report provides new insights on the mechanisms contributing to the reciprocal and/or bilateral regulations of nigrostriatal dopaminergic pathways.

The role of dopamine released from distal and proximal dendrites of nigrostriatal dopaminergic neurons in the control of GABA transmission in the thalamic nucleus ventralis medialis in the cat.

Halothane-anaesthetized cats implanted with push-pull cannulae were used in this study. Amphetamine was applied in the pars reticulata or pars compacta of the substantia nigra in order to determine the role of dopamine released from distal or proximal dendrites of dopaminergic cells in the control of GABAergic transmission in the nucleus ventralis medialis of the thalamus. When applied for 30 min in either the pars reticulata or the pars compacta, amphetamine (10(-6) M) enhanced to a similar extent the local release of [3H]dopamine synthesized from [3H]tyrosine, these effects being seen mainly during the drug application. The amphetamine-evoked release of dopamine in the pars reticulata produced a long lasting reduction in the release of [3H]GABA synthesized from [3H]glutamine in the nucleus ventralis medialis as well as in the paralamellar zone of the nucleus ventralis lateralis. Opposite effects were observed when amphetamine (10(-6) M) was applied in the pars compacta. In complementary experiments, single unit recordings were made in the intermediate part of the pars reticulata, some of the cells being identified by antidromic activation from the nucleus ventralis medialis. Whether applied in the pars reticulata or pars compacta, amphetamine (10(-6) M, 10 min) evoked a reversible decrease in the firing rate of most recorded cells whether or not they were identified as projecting to the nucleus ventralis medialis. Therefore, the decreased release of [3H]GABA in the nucleus ventralis medialis seen following application of amphetamine in the pars reticulata of the substantia nigra could result from an inhibition of nigrothalamic GABAergic neurons. Since the nucleus ventralis medialis is also innervated by GABAergic neurons originating in the entopeduncular nucleus, single unit recordings were made from cells in this nucleus during the application of amphetamine (10(-6) M, 10 min) into the pars compacta of the substantia nigra, some of which were identified antidromically as projecting to the nucleus ventralis medialis. Most cells identified or not were found to be activated during this treatment. These results suggested that the increased release of [3H]GABA seen in the nucleus ventralis medialis following application of amphetamine in the pars compacta of the substantia nigra might be linked to the enhanced firing rate of entopeduncular-thalamic GABAergic neurons.

Effects of nigral application of muscimol on release of [3H] gamma-aminobutyrate and on multiunit activity in various cat thalamic nuclei.

The release of [3H] gamma-aminobutyrate (GABA) neosynthesized from [3H]glutamine was estimated in one substantia nigra and in the ipsilateral thalamus of halothane-anesthetized cats by perfusing a [3H]glutamine-enriched physiological medium through a push-pull cannula implanted in the two structures under investigation. After two hours of superfusion, muscimol (10(-6)M) was delivered through the nigral push-pull cannula for 50-60 min and local- and distal-evoked changes of [3H]GABA release were analyzed. In some experiments, changes of global neuronal activity induced by muscimol application were recorded in different thalamic nuclei, using a bipolar electrode. In a few of the above experiments, biochemical and electrophysiological determinations were simultaneously performed in the substantia nigra and the thalamus. The nigral application of muscimol (10(-6)M) induced locally an activation of the substantia nigra reticulata cells, as well as an increase in release of [3H]GABA. Distally, in the thalamus, two types of biochemical and electrophysiological responses were observed according to the localization of the tip of the push-pull cannula or the electrode. (1) An increased release of [3H]GABA and a depression of the global multi-unit cellular activity were obtained in the ventralis medialis-ventralis lateralis, the centralis lateralis and the paracentralis nuclei. These effects could reflect an activation of the GABAergic nigrothalamic neurons projecting to these different thalamic nuclei. (2) In contrast, in the medialis dorsalis paralamellar zone adjacent to the intralaminar nuclei of the thalamus, a decrease of [3H]GABA release and an activation of the multi-unit activity were obtained. These latter results may suggest either a polysynaptic response or the non-GABAergic nature of the nigrothalamic neurons afferent to the medialis dorsalis paralamellar zone.

Somatosensory input to dopamine neurones of the monkey midbrain: responses to pain pinch under anaesthesia and to active touch in behavioural context.

The somatosensory responses of single dopamine (DA) neurones were recorded in the pars compacta of substantia nigra and in neighbouring DA cell groups of four Macaca fascicularis monkeys. These neurones were electrophysiologically discriminated against other cells by their polyphasic, relatively long impulses (2.0-5.0 ms) occurring at low rates (mostly 1.0-5.0/s), by antidromic activation from caudate or putamen, and by reduction of impulse rate following subcutaneous injection of apomorphine (0.05-0.15 mg/kg). Of 140 DA neurones recorded in two monkeys under barbiturate anaesthesia, 51% showed reductions and 17% increases in impulse rate during intense noxious pinch stimulation. Neurones responded non-somatotopically to stimulation of the hand, foot, face, dorsum and tail on both sides of the body. Innocuous, even intense, surface or deep somatosensory stimuli were ineffective. Systemic injection of the DA receptor antagonist haloperidol (0.33-0.5 mg/kg) strongly reduced the pinch responses. Of 154 DA neurones recorded in two monkeys during self-initiated arm movements, 84% showed phasic activations with latencies of 65 ms when the monkey's hand touched a food morsel inside the target box. Responses were absent when touching other objects. Touch responses to food did not occur when the reaching movement into the same food box was performed in reaction to an external trigger stimulus. In conclusion, DA neurones were activated in specific behavioural contexts by somatosensory stimuli of low intensities while responding unconditionally to noxious input.