Spinal gunshot wounds: A retrospective, multicenter, cohort study. / [Artículo traducido] Lesiones vertebrales por proyectil de arma de fuego: estudio de cohorte retrospectivo, multicéntrico.

INTRODUCTION AND OBJECTIVE: To describe the demographic and clinical characteristics and treatment of patients with spinal gunshot wounds across Latin America. MATERIAL AND METHODS: Retrospective, multicenter cohort study of patients treated for gunshot wounds to the spine spanning 12 institutions across Latin America between January 2015 and January 2022. Demographic and clinical data were recorded, including the time of injury, initial assessment, characteristics of the vertebral gunshot injury, and treatment. RESULTS: Data on 423 patients with spinal gunshot injuries were extracted from institutions in Mexico (82%), Argentina, Brazil, Colombia, and Venezuela. Patients were predominantly male civilians in low-risk-of-violence professions, and of lower/middle social status, and a sizeable majority of gunshots were from low-energy firearms. Vertebral injuries mainly affected the thoracic and lumbar spine. Neurological injury was documented in 320 (76%) patients, with spinal cord injuries in 269 (63%). Treatment was largely conservative, with just 90 (21%) patients treated surgically, principally using posterior open midline approach to the spine (79; 87%). Injury features distinguishing surgical from non-surgical cases were neurological compromise (P = 0.004), canal compromise (P < 0.001), dirty wounds (P < 0.001), bullet or bone fragment remains in the spinal canal (P < 0.001) and injury pattern (P < 0.001). After a multivariate analysis through a binary logistic regression model, the aforementioned variables remained statistically significant except neurological compromise. CONCLUSIONS: In this multicenter study of spinal gunshot victims, most were treated non-surgically, despite neurological injury in 76% and spinal injury in 63% of patients.

Spinal gunshot wounds: A retrospective, multicenter, cohort study.

INTRODUCTION AND OBJECTIVE: To describe the demographic and clinical characteristics and treatment of patients with spinal gunshot wounds across Latin America. MATERIAL AND METHODS: Retrospective, multicenter cohort study of patients treated for gunshot wounds to the spine spanning 12 institutions across Latin America between January 2015 and January 2022. Demographic and clinical data were recorded, including the time of injury, initial assessment, characteristics of the vertebral gunshot injury, and treatment. RESULTS: Data on 423 patients with spinal gunshot injuries were extracted from institutions in Mexico (82%), Argentina, Brazil, Colombia, and Venezuela. Patients were predominantly male civilians in low-risk-of-violence professions, and of lower/middle social status, and a sizeable majority of gunshots were from low-energy firearms. Vertebral injuries mainly affected the thoracic and lumbar spine. Neurological injury was documented in n=320 (76%) patients, with spinal cord injuries in 269 (63%). Treatment was largely conservative, with just 90 (21%) patients treated surgically, principally using posterior open midline approach to the spine (n=79; 87%). Injury features distinguishing surgical from non-surgical cases were neurological compromise (p=0.004), canal compromise (p<0.001), dirty wounds (p<0.001), bullet or bone fragment remains in the spinal canal (p<0.001) and injury pattern (p<0.001). After a multivariate analysis through a binary logistic regression model, the aforementioned variables remained statistically significant except neurological compromise. CONCLUSIONS: In this multicenter study of spinal gunshot victims, most were treated non-surgically, despite neurological injury in 76% and spinal injury in 63% of patients.

Protective Mechanisms of Butyrate on Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a multifactorial chronic disease, commonly associated with alteration in the composition and function of gut microbiota. This process can lead to a decreased production of short chain fatty acids (SCFAs) by the gut microbiota, mainly butyrate, which is an important immunomodulatory molecule in the intestine. Butyrogenic bacteria normally produces butyrate through carbohydrate fermentation or amino acids degradation pathways. This molecule plays an important protective role in intestinal homeostasis acting in both adaptive immunity and innate immunity. This review summarizes the current knowledge about the role of butyrate on the development of IBD and the protective mechanisms of this metabolite on the intestinal mucosa and the whole body, as reported by in vitro and in vivo studies. Thus, butyrate can regulate the activation of regulatory T cells, increasing the acetylation of histones and decreasing the activation of NF-κB. In addition, it can also stimulate the mucus production from epithelial cells and the rearrangement of tight junction proteins.

Estudio de componentes hemolinfáticos de Rhodnius prolixus y Triatoma maculata alimentados con diferentes fuentes sanguíneas / Study of hemolymphatic components of Rhodnius prolixus and Triatoma maculata fed on different blood sources

RESUMEN Introducción: Tradicionalmente, Rhodnius prolixus ha sido considerado el principal vector, mientras que Triatoma maculata resulta ser un vector secundario de Trypanosoma cruzi en el medio rural venezolano. En este trabajo se provee información de interés acerca de los componentes bioquímicos y del sistema inmune, humoral y celular, de la hemolinfa de R. prolixus y T. maculata alimentados sobre gallina y rata. Metodología: los insectos provenían de una colonia del laboratorio, mantenida a una temperatura de 27-29ºC, 50% de humedad relativa y ocho horas luz/día. Se analizó la hemolinfa de adultos alimentados sobre gallina y rata. Se observaron los hemocitos mediante microscopía óptica y electrónica de transmisión. Resultados: los parámetros bioquímicos de glucosa, lípidos y proteínas fueron afectados de forma distinta en R. prolixus y T. maculata según la fuente alimenticia. T. maculata presentó mayores niveles de actividad lítica de lisozima. Se observaron cuatro poblaciones de hemocitos (prohemocitos, plasmatocitos, granulocitos y oenocitos), cuyas características y medidas están acorde a lo reportado por otros autores sobre la subfamilia Triatominae. T. maculata presentó mayor número de prohemocitos y oenocitos que R. prolixus. Conclusiones: En su hemolinfa, R. prolixus y T. maculata son afectados distintamente en los componentes bioquímicos (glucosa, lípidos y proteínas) e inmunes, tanto humorales (lizosima) como celulares (prohemocitos, oenocitos), según sean alimentados sobre gallina y rata. Esto pone de manifiesto de la alimentación sobre uno de los componentes de la competencia vectorial, como lo es el sistema inmune propio de la hemolinfa de los insectos.

ABSTRACT Introduction: Traditionally, Rhodnius prolixus has been considered the main vector, while Triatoma maculata remains to be a secondary vector of Trypanosoma cruzi in the Venezuelan rural habitat. In this work, interesting information about the biochemical and immune (humoral and cellular) aspects of the hemolymph of R. prolixus and T. maculate, feeding on hen and rat, are presented. Methodology: Hemolymph was extracted from adult insects, maintained at 2729 °C with 50% of relative humidity and 8/16 (Light/Dark) hours, and fed on hen and rat. Hemocytes were observed by optical and transmission electron microscopy. Results: Biochemical parameters (glucose, lipids and proteins) varied in both species according to the food source. T. maculata presented higher levels of lysozyme lytic activity. Four hemocytes populations were observed by optical and transmission electron microscopy (prohemocytes, plasmocytes, granulocytes and oenocytes), exhibiting characteristics and measurements in accordance with previous literature related to the Triatominae subfamily. T maculata presented more prohemocytes and oenocytes than R. prolixus. Conclusions: On their hemolymph, R. prolixus and T. maculata are distinctly affected in their biochemical (glucose, lipids and proteins) and immune components, both humoral (lysozyme) and cellular (prohemocytes, oenocytes), depending on whether they were fed on hens or rats. Our results show that the food source affects the immune system of triatomines, and subsequently, their vectorial capacity may be compromised as well.

Uso de la fluorescencia cercana al infrarrojo en nefrectomía parcial laparoscópica asistida por robot / Use of near infrared fluorescence during robot-assisted laparoscopic partial nephrectomy

Antecedentes: La nefrectomía parcial es el tratamiento de elección para tumores T1a, siendo el abordaje abierto aún el estándar. La cirugía laparoscópica asistida por robot ofrece ventajas aplicables a la nefrectomía parcial como el uso del sistema Firefly® con fluorescencia cercana al infrarrojo. Objetivo: Mostrar la aplicación de la fluorescencia en una cirugía preservadora de nefronas. Caso clínico: Mujer de 37 años, fumadora, con obesidad. Tumor renal derecho de 31 mm como hallazgo en tomografía por lo que es sometida a nefrectomía parcial laparoscópica asistida por robot, con tiempo de isquemia caliente de 22 minutos y uso de fluorescencia con sistema Firefly® para guiar la resección, sin complicaciones, con carcinoma de células renales pT1aN0M0, márgenes negativos. La cirugía renal laparoscópica asistida por robot se emplea para cirugía preservadora de nefronas, con buenos resultados oncológicos y funcionales. La combinación de la tecnología Firefly® con el ultrasonido transoperatorio puede delimitar con mayor precisión la extensión de la lesión, pudiendo aumentar los márgenes negativos y disminuir el tiempo de isquemia. Conclusión: La fluorescencia cercana al infrarrojo en la nefrectomía parcial asistida por robot es útil para guiar la resección del tumor y potencialmente poder mejorar los resultados oncológicos y funcionales

Background: Partial nephrectomy is the treatment of choice for T1a tumours. The open approach is still the standard method. Robot-assisted laparoscopic surgery offers advantages that are applicable to partial nephrectomy, such as the use of the Firefly® system with near-infrared fluorescence. Objective: To demonstrate the implementation of fluorescence in nephron-sparing surgery. Case report: This case concerned a 37-year-old female smoker, with obesity. The patient had a right kidney tumour measuring 31 mm, which was found using tomography. She therefore underwent robot-assisted laparoscopic partial nephrectomy, with a warm ischaemia time of 22 minutes and the use of fluorescence with the Firefly® system to guide the resection. There were no complications. The tumour was a pT1aN0M0 renal cell carcinoma, with negative margins. Robot-assisted renal laparoscopic surgery is employed for nephron-sparing surgery, with good oncological and functional results. The combination of the Firefly® technology and intraoperative ultrasound can more accurately delimit the extent of the lesion, increase the negative margins and decrease the ischaemia time. Conclusion: Near-infrared fluorescence in robot-assisted partial nephrectomy is useful for guiding the tumour resection and can potentially improve the oncological and functional results

Use of near infrared fluorescence during robot-assisted laparoscopic partial nephrectomy.

BACKGROUND: Partial nephrectomy is the treatment of choice for T1a tumours. The open approach is still the standard method. Robot-assisted laparoscopic surgery offers advantages that are applicable to partial nephrectomy, such as the use of the Firefly® system with near-infrared fluorescence. OBJECTIVE: To demonstrate the implementation of fluorescence in nephron-sparing surgery. CASE REPORT: This case concerned a 37-year-old female smoker, with obesity. The patient had a right kidney tumour measuring 31 mm, which was found using tomography. She therefore underwent robot-assisted laparoscopic partial nephrectomy, with a warm ischaemia time of 22 minutes and the use of fluorescence with the Firefly® system to guide the resection. There were no complications. The tumour was a pT1aN0M0 renal cell carcinoma, with negative margins. Robot-assisted renal laparoscopic surgery is employed for nephron-sparing surgery, with good oncological and functional results. The combination of the Firefly® technology and intraoperative ultrasound can more accurately delimit the extent of the lesion, increase the negative margins and decrease the ischaemia time. CONCLUSION: Near-infrared fluorescence in robot-assisted partial nephrectomy is useful for guiding the tumour resection and can potentially improve the oncological and functional results.

Neutron spectra at two beam ports of a TRIGA Mark III reactor loaded with HEU fuel.

The neutron spectra have been measured in two beam ports, one radial and another tangential, of the TRIGA Mark III nuclear reactor from the National Institute of Nuclear Research in Mexico. Measurements were carried out with the reactor core loaded with high enriched uranium fuel. Two reactor powers, 5 and 10 W, were used during neutron spectra measurements using a Bonner sphere spectrometer with a (6)LiI(Eu) scintillator and 2, 3, 5, 8, 10 and 12 in.-diameter high-density polyethylene spheres. The neutron spectra were unfolded using the NSDUAZ unfolding code. For each spectrum total flux, mean energy and ambient dose equivalent were determined. Measured spectra show fission, epithermal and thermal neutrons, being harder in the radial beam port.

Concrete enclosure for shielding a neutron source.

In the aim to design a shielding for a 0.185 TBq (239)PuBe isotopic neutron source several Monte Carlo calculations were carried out using MCNP5 code. First, a point-like source was modeled in vacuum and the neutron spectrum and ambient dose equivalent were calculated at several distances ranging from 5 cm up to 150 cm, these calculations were repeated modeling a real source, including air, and a 1×1×1 m(3) enclosure with 5, 15, 20, 25, 30, 50 and 80 cm-thick Portland type concrete walls. At all the points located inside the enclosure neutron spectra from 10(-8) up to 0.5 MeV were the same regardless the distance from the source showing the room-return effect in the enclosure, for energies larger than 0.5 MeV neutron spectra are diminished as the distance increases. Outside the enclosure it was noticed that neutron spectra becomes "softer" as the concrete thickness increases due to reduction of mean neutron energy. With the ambient dose values the attenuation curve in terms of concrete thickness was calculated.

Water-extended polyester neutron shield for a 252Cf neutron source.

A Monte Carlo study to determine the shielding features to neutrons of water-extended polyester was carried out. During calculations, (252)Cf and shielding were modelled and the neutron spectra as well as the H(10) were calculated in four sites. The calculation was extended to include a water shielding, the source in vacuum and in air. Besides neutron shielding characteristics, the Kerma in air due to gammas emitted by (252)Cf and due to capture gamma rays in the shielding were included.

Artificial neural networks technology for neutron spectrometry and dosimetry.

Artificial Neural Network Technology has been applied to unfold neutron spectra and to calculate 13 dosimetric quantities using seven count rates from a Bonner Sphere Spectrometer with a (6)LiI(Eu). Two different networks, one for spectrometry and another for dosimetry, were designed. To train and test both networks, 177 neutron spectra from the IAEA compilation were utilised. Spectra were re-binned into 31 energy groups, and the dosimetric quantities were calculated using the MCNP code and the fluence-to-dose conversion coefficients from ICRP 74. Neutron spectra and UTA4 response matrix were used to calculate the expected count rates in the Bonner spectrometer. Spectra and H(10) of (239)PuBe and (241)AmBe were experimentally obtained and compared with those determined with the artificial neural networks.

Neutron fluence rate measurement using prompt gamma rays.

A gamma ray spectrometer, with a 3('') Ø X 3('') NaI(Tl) detector, with a moderator sphere has been utilised to measure the neutron fluence rate, with this value the H(10) was estimated. When a neutron is captured by the hydrogen-based moderator, a 2.22 MeV prompt gamma ray is produced. In a multichannel analyser the net area under the 2.22 MeV photopeak is proportional to the total neutron fluence rate. The features of this system were determined by a Monte Carlo study that includes 3-, 5- and 10-inches diameter, water and polyethylene moderators and a (239)Pu-Be source. The prompt gamma response was extended to monoenergetic neutron sources. To verify the response, a (239)Pu-Be source in combination with a 10('') polyethylene sphere having a gamma-ray spectrometer with NaI(Tl) was utilised to estimate the neutron fluence rate and the H(10). These results were compared with neutron fluence rate and H(10) obtained using a Bonner sphere spectrometer and with the H(10) measured using a neutron remmeter.

Artificial neural networks in neutron dosimetry.

An artificial neural network (ANN) has been designed to obtain neutron doses using only the count rates of a Bonner spheres spectrometer (BSS). Ambient, personal and effective neutron doses were included. One hundred and eighty-one neutron spectra were utilised to calculate the Bonner count rates and the neutron doses. The spectra were transformed from lethargy to energy distribution and were re-binned to 31 energy groups using the MCNP 4C code. Re-binned spectra, UTA4 response matrix and fluence-to-dose coefficients were used to calculate the count rates in the BSS and the doses. Count rates were used as input and the respective doses were used as output during neural network training. Training and testing were carried out in the MATLAB environment. The impact of uncertainties in BSS count rates upon the dose quantities calculated with the ANN was investigated by modifying by +/-5% the BSS count rates used in the training set. The use of ANNs in neutron dosimetry is an alternative procedure that overcomes the drawbacks associated with this ill-conditioned problem.

Protocolo en pacientes pediátricos con neumonía adquirida en la comunidad: julio 2001-enero 2002 / Protocol in patient pediatric with pneumonia acquired in the community: july 2001-january 2002

Aplicar las recomendaciones terapéuticas establecidas por la Sociedad Venezolana de Infectología y observar los efectos en pacientes pediátricos con neumonía adquirida en la comunidad. Departamento de Pediatría. Servicio Autónomo del Hospital Central de Maracay. Estudio prospectivo, exploratorio. Las recomendaciones fueron aplicadas a 71 pacientes pediátricos con neumonía adquirida en la comunidad ingresados durante julio 2001-enero 2002, analizando al ingreso las variables: edad, sexo, Rx. de tórax, hemocultivo, Phadebact® de orina; y al ingreso más al tercer día: temperatura, frecuencia respiratoria, tiraje, vómitos, hematología completa y velocidad de sedimentación globular. Tratados: Penicilina Cristlina 250.000-400.000 U/kg/día. Se excluyeron aquellos que recibieron antimicrobianos diferentes a amoxicilina durante las primeras 72 horas previas al ingreso y los primeros días de hospitalización o con neumonías complicadas. Los Datos fueron recopilados en fichas, llevados a una base de datos, tabulados y analizados porcentualmente. La mayor frecuencia correspondió a menores de 6 años. El sexo más afectado: masculino 3:1. Clínica al ingreso: Taquipnea: 64,79 por ciento, tiraje 61,97 por ciento, fiebre 47,07 por ciento e intolerncia a la vía oral 15,49 por ciento. Reactantes de la fase aguda. Leucocitosis 100 por ciento, neutrofilia 70 por ciento y velocidad de sedimentación globular incrementada en partes. Después de 72 horas los resultados son positivos ante la práctica de esta conducta evidenciándose mejoría. Hemocultivos reportaron 100 por ciento negatividad, de 14 Phadebact® de orina positivos, el germen más frecuente: Streptococcus pneumoniae 57,14 por ciento con sensibilidad a la penicilina igualmente que Nesseria meningitides, siendo Haemophilus influenzae resistente. Radiológicamente la localización segmentaria estuvo en más del 50 por ciento. Estancia hospitalaria media: 4,74. Penicilina cristalina como tratamiento de elección establecido.

Antioxidant effects of an aqueous extract of Ilex paraguariensis.

In this work we investigate the antioxidant properties of an aqueous extract prepared from an infusion of Ilex paraguariensis (Aquifoliaceae) using free radical-generating systems. The extract inhibited the enzymatic and nonenzymatic lipid peroxidation in rat liver microsomes in a concentration-dependent fashion, with IC(50) values of 18 microg/ml and 28 microg/ml, respectively. The extract also inhibited the H(2)O(2)-induced peroxidation of red blood cell membranes with an IC(50) of 100 microg/ml and exhibited radical scavenging properties toward superoxide anion (IC(50) = 15 microg/ml) and 2,2-diphenyl-1-picrylhydrazyl radical. In the range of concentrations used, the extract was not a scavenger of the hydroxyl radical. Our results suggest that ingestion of extracts of Ilex paraguariensis could contribute to increase the antioxidant defense of an organism against free radicals attack.

A synergistic neurotrophic response to l-dihydroxyphenylalanine and nerve growth factor.

The catecholamine precursor l-dihydroxyphenylalanine (L-DOPA) is the primary therapeutic intervention for Parkinson's disease. Although short-term exposure (30 min) potentiates dopamine (DA) release by elevating quantal size, longer term exposure to L-DOPA (48 hr) promotes neurite outgrowth from midbrain DA neurons in culture. To characterize long term effects of L-DOPA, we used a pheochromocytoma (PC12) line that extends neurites on exposure to nerve growth factor (NGF). L-DOPA potentiated the outgrowth of processes elicited by NGF. This response did not require conversion of L-DOPA to DA, was not caused by agonist effects at DA receptors, and was not blocked by the tyrosine kinase inhibitor genistein. However, similar results were found after exposure to l-n-acetylcysteine or apomorphine, a DA receptor agonist that produces a quinone metabolite, and seemed to correlate with glutathione synthesis. Long-term process elaboration was blocked by L-buthionine sulfoximine, consistent with mediation by an antioxidant mechanism. L-DOPA potentiation of NGF response was important functionally as seen by increased quantal neurotransmitter release from the L-DOPA/NGF-treated neurite varicosities, which displayed both 2-fold greater quantal size and frequency of quantal release. These results demonstrate potentiation by L-DOPA of morphological and physiological responses to neurotrophic factors as well as synergistic induction of antioxidant pathways. Together with effects on transmitter synthesis, these properties seem to provide a basis for the compound's long term presynaptic potentiation of DA release and therapeutic actions.

D2-Like dopamine autoreceptor activation reduces quantal size in PC12 cells.

D2-like dopamine autoreceptors regulate dopamine release and are implicated in important actions of antipsychotic drugs and rewarding behaviors. To directly observe the effects of D2 autoreceptors on exocytic neurotransmitter release, we measured quantal release of dopamine from pheochromocytoma PC12 cells that express D2 and D4 autoreceptors. High potassium-evoked secretion in PC12 cells produced a unimodal population of quantal sizes. We found that exposures to the D2-like agonist quinpirole that inhibited tyrosine hydroxylase activity by approximately 50% also reduced quantal size by approximately 50%. The reduced quantal size was blocked by the D2 antagonist sulpiride and reversed by L-DOPA. Quinpirole also decreased the frequency of stimulation-evoked quantal release. Together, these findings indicate effects on quantal neurotransmission by D2-like dopamine autoreceptors previously distinguished as synthesis-modulating autoreceptors that regulate tyrosine hydroxylase activity versus impulse-regulating autoreceptors that modulate membrane potential. The results also provide an initial demonstration of a receptor-mediated mechanism that alters quantal size.

Presynaptic recording of quanta from midbrain dopamine neurons and modulation of the quantal size.

The observation of quantal release from central catecholamine neurons has proven elusive because of the absence of evoked rapid postsynaptic currents. We adapted amperometric methods to observe quantal release directly from axonal varicosities of midbrain dopamine neurons that predominantly contain small synaptic vesicles. Quantal events were elicited by high K+ or alpha-latrotoxin, required extracellular Ca2+, and were abolished by reserpine. The events indicated the release of 3000 molecules over 200 microsec, much smaller and faster events than quanta associated with large dense-core vesicles previously recorded in vertebrate preparations. The number of dopamine molecules per quantum increased as a population to 380% of controls after glial-derived neurotrophic factor (GDNF) exposure and to 350% of controls after exposure to the dopamine precursor L-dihydroxyphenylalanine (L-DOPA). These results introduce a means to measure directly the number of transmitter molecules released from small synaptic vesicles of CNS neurons. Moreover, quantal size was not an invariant parameter in CNS neurons but could be modulated by neurotrophic factors and altered neurotransmitter synthesis.

Voltammetric and pharmacological characterization of dopamine release from single exocytotic events at rat pheochromocytoma (PC12) cells.

Although rat pheochromocytoma (PC12) neurotransmitter storage vesicles are known to contain a variety of neurotransmitters including catecholamines, there is little evidence that the molecular species detected during amperometric monitoring of exocytosis is a catecholamine. Rather, as these are catecholamine-containing cells, one assumes catecholamines are released. Additionally, although the total amount of transmitter released can be quantified, it has been extremely difficult to evaluate the concentration at the point of release for each exocytosis event. Interpreting voltammograms obtained in the attoliter volume affected between the electrode and the cell and defined by the size of the exocytosis pore during exocytosis is an extreme analytical challenge. Here we use voltammetry of approximately 10(-19) mol released from individual exocytosis events to identify, along with pharmacological evidence, the released compound at PC12 cells as a catecholamine, most likely dopamine. The area of the electrode at which oxidation occurs following an exocytosis event is proportional to the temporal delay prior to acquisition of a voltammogram. This model allows determination of relative concentrations from individual release events and has been used to examine events at control cells and cells incubated with the dopamine precursor, L-3,4-dihydroxyphenylalanine (L-DOPA). Exposure to L-DOPA (100 microM for 1 h) results in 145 detectable events for 11 cells compared to 77 events for 29 control cells, clearly indicating that vesicles can be "loaded" with dopamine. However, the concentrations measured at the electrode surface provide similar distributions for both L-DOPA-treated and control cells. Cyclic voltammetric measurements of relative concentration for zeptomole levels of transmitter in attoliter volumes provide evidence that loading vesicles by increased transmitter synthesis does not lead to elevated concentrations at individual release sites.

Neurotrophic effects of L-DOPA in postnatal midbrain dopamine neuron/cortical astrocyte cocultures.

L-DOPA is toxic to catecholamine neurons in culture, but the toxicity is reduced by exposure to astrocytes. We tested the effect of L-DOPA on dopamine neurons using postnatal ventral midbrain neuron/cortical astrocyte cocultures in serum-free, glia-conditioned medium. L-DOPA (50 microM) protected against dopamine neuronal cell death and increased the number and branching of dopamine processes. In contrast to embryonically derived glia-free cultures, where L-DOPA is toxic, postnatal midbrain cultures did not show toxicity at 200 microM L-DOPA. The stereoisomer D-DOPA (50-400 microM) was not neurotrophic. The aromatic amino acid decarboxylase inhibitor carbidopa (25 microM) did not block the neurotrophic effect. These data suggest that the neurotrophic effect of L-DOPA is stereospecific but independent of the production of dopamine. However, L-DOPA increased the level of glutathione. Inhibition of glutathione peroxidase by L-buthionine sulfoximine (3 microM for 24 h) blocked the neurotrophic action of L-DOPA. N-Acetyl-L-cysteine (250 microM for 48 h), which promotes glutathione synthesis, had a neurotrophic effect similar to that of L-DOPA. These data suggest that the neurotrophic effect of L-DOPA may be mediated, at least in part, by elevation of glutathione content.