Assessing the effect of antimony pressure on trypanothione reductase activity in Leishmania (Viannia) braziliensis.

Leishmania parasites have an oxidative and chemical defense mechanism called trypanothione system (T[SH]2), the most abundant thiol system in trypanosomatids. This system has a central role in processing pentavalent antimony and resistance has been related to a better capacity to metabolize it through the activation of T[SH]2 enzymatic cascade. A biochemical approach was applied to assess the effect of trivalent (SbIII) and pentavalent antimony (SbV) on Trypanothione Reductase (TR) activity of two Leishmania (Viannia) braziliensis clinical isolates, which were labeled as responder (R) and non-responder (NR) after patient treatment with Glucantime®. Both isolates were characterized based on in vitro susceptibility to SbIII and SbV and trypanothione reductase (TR) activity. SbIII and SbV discriminated susceptibility profiles in all parasite forms, since isolate NR had significantly higher EC50 values than isolate R. Differences were observed in TR activity between promastigotes, axenic amastigotes and intracellular amastigotes: R (0.439 ± 0.009, 0.103 ± 0.01 and 0.185 ± 0.01AU.min-1.µg of protein-1) and NR (1.083 ± 0.04, 0.914 ± 0.04 and 0.343 ± 0.04 AU. min-1.µg of protein-1), respectively. Incubation with SbIII and SbV using each form EC50 value caused a time-dependent differential effect on TR activity suggesting that oxidative defense is related to the antimony susceptibility phenotype. Data gathered here shows a biochemical approach able to discriminate two L. (V.) braziliensis clinical isolates measurements TR activity of promastigotes, axenic amastigotes and intracellular amastigotes.

The potential of live attenuated vaccines against Cutaneous Leishmaniasis.

Cutaneous Leishmaniasis is a serious public health problem, typically affecting poor populations with limited access to health care. Control is largely dependent on chemotherapies that are inefficient, costly and challenging to deliver. Vaccination is an attractive and feasible alternative because long-term protection is typical in patients who recover from the disease. No human vaccine is yet approved for use, but several candidates are at various stages of testing. Live attenuated parasites, which stimulate long-term immune protection, have potential as effective vaccines, and their challenges relating to safety, formulation and delivery can be overcome. Here we review current data on the potential of live attenuated Leishmania vaccines and discuss possible routes to regulatory approval.

Cellular localization and distribution of dopamine D(4) receptors in the rat cerebral cortex and their relationship with the cortical dopaminergic and noradrenergic nerve terminal networks.

The role of the dopamine D(4) receptor in cognitive processes and its association with several neuropsychiatric disorders have been related to its preferential localization in the cerebral cortex. In the present work we have studied in detail the regional and cellular localization of the dopamine D(4) receptor immunoreactivity (IR) in the rat cerebral cortex and its relationship to the dopaminergic and noradrenergic nerve terminal networks, since both dopamine and noradrenaline have a high affinity for this receptor. High levels of D(4) IR were found in motor, somatosensory, visual, auditory, temporal association, cingulate, retrosplenial and granular insular cortices, whereas agranular insular, piriform, perirhinal and entorhinal cortices showed low levels. D(4) IR was present in both pyramidal and non-pyramidal like neurons, with the receptor being mainly concentrated to layers II/III. Layer I was observed to be exclusively enriched in D(4) IR branches of apical dendrites. Finally, mismatches were observed between D(4) IR and tyrosine hydroxylase and dopamine beta-hydroxylase IR nerve terminal plexuses, indicating that these receptors may be activated at least in part by dopamine and noradrenaline operating as volume transmission signals. The present findings support a major role of the dopamine D(4) receptor in mediating the transmission of cortical dopamine and noradrenaline nerve terminal plexuses.

Cáncer de mama con invasión metastásica del Ganglio Centinela en cadena mamaria interna y cadenas axilares libres de lesión tumoral / Breast cancer with metastatic invasion of the sentinel lymph node in an internal mammary chain and with axillary chains free of tumoral lesion

La linfogammagrafía es un método ampliamente aceptado para la detección del Ganglio Centinela en cáncer de mama. Presentamos el caso de una mujer de 45 años de edad diagnosticada de neoplasia de mama, la cual es remitida a la sección de Medicina Nuclear para llevar a cabo la técnica de detección del Ganglio Centinela. La linfogammgrafía realizada previamente a la intervención quirúrgica muestra una doble migración del radiotrazador que se dirige por una parte a la axila y, por otra, a la cadena mamaria interna. Cada una de estas áreas presentó un Ganglio Centinela. Tras la extracción de los mismos, el análisis anatomopatológico reveló infiltración metastásica del Ganglio Centinela ubicado en la cadena mamaria interna, mientras que el axilar y todos los nodos obtenidos del vaciamiento se mostraron libres de células tumorales. La conclusión de este caso es que se debe realizar la extracción y análisis de todos los Ganglios Centinela detectados. (AU)

Practice of nuclear medicine in Spain.

This survey presents the results of a poll sent to all Spanish nuclear medicine departments between July 1999 and March 2000, with the aim of clarifying the current situation of nuclear medicine in Spain. This survey is believed to be the first of its kind, and it is anticipated that the data will be of assistance to health authorities in ensuring that the needs of the population with regard to nuclear medicine facilities are met.

[Breast cancer with metastatic invasion of the sentinel lymph node in an internal mammary chain and with axillary chains free of tumor lesionS]. / Cáncer de mama con invasión metastásica del ganglio centinela en cadena mamaria interna y cadenas axilares libres de lesión tumoral.

The lymphoscintigraphy is a widely accepted procedure to detect the sentinel node in breast cancer. This is a case report of a 45 year old woman diagnosed of breast cancer who was referred to the nuclear medicine facility to perform the sentinel node detection procedure. The lymphoscintigraphy prior to surgery shows a double pathway in the tracer migration: one going to the axillary area and the second to the internal mammary chain and shows hot spots that represent the sentinel nodes. After surgical removal of those nodes, the pathological analysis report indicated tumor infiltration in the internal mammary chain sentinel node with all axillary nodes free of malignant cells. The aim of this report is to emphasize the importance of performing a pathological analysis of all the sentinel nodes detected in lymphoscintigraphy.

Dopamine D5 receptors of rat and human brain.

In contrast to dopamine D1 receptors, the anatomical distribution of D5 receptors in the CNS is poorly described. Therefore, we have studied the localization of dopamine D5 receptors in the brain of rat and human using our newly prepared subtype-specific antibody. Western blot analysis of brain tissues and membranes of cDNA transfected cells, and immunoprecipitation of brain dopamine receptors suggest that this antibody is highly selective for native dopamine D5 receptors. The D5 antibody labeled dopaminergic neurons of mesencephalon, and cortical and subcortical structures. In neostriatum, the D5 receptors were localized in the medium spiny neurons and large cholinergic interneurons. The D5 labeling in caudate nucleus was predominantly in spines of the projection neurons that were frequently making asymmetric synapses. Occasionally, the D5 receptors were also found at the symmetric synapses. Within the cerebral cortex and hippocampus, D5 antibody labeling was prominent in the pyramidal cells and their dendrites. Dopamine D5 receptors were also prominent in the cerebellum, where dopamine innervation is known to be very modest. Differences in the localization of D5 receptors between both species were generally indistinguishable except in hippocampus. In rat, the hippocampal D5 receptor was concentrated in the cell body, whereas in human it was also associated with dendrites. These results show that D5 receptors are localized in the substantia nigra-pars compacta, hypothalamus, striatum, cerebral cortex, nucleus accumbens and olfactory tubercle. Furthermore, the presence of D5 receptors in the areas of dopamine pathways suggests that this receptor may participate actively in dopaminergic neurotransmission.

Falso positivo en la detección de un divertículo de Meckel / False positives in the detection of Meckel diverticulum

No disponible

Incidence of gastroesophageal reflux and aspiration in mechanically ventilated patients using small-bore nasogastric tubes.

BACKGROUND: Use of a large-bore nasogastric tube (NGT) and patient position are considered key factors in promoting gastroesophageal reflux (GER) and pulmonary aspiration in critically ill patients. The objective of this study was to determine the incidence of GER and pulmonary aspiration of gastric contents in mechanically ventilated (MV) patients using small-bore NGTs. METHODS: We studied 30 patients on mechanical ventilation for acute respiratory failure who tolerated enteral nutrition through a small-bore NGT. Patients were randomly assigned to a group with (n = 16) or without (n = 14) a small-bore NGT and were maintained in a semirecumbent position during the study. GER and aspiration of gastric contents were assessed by a radioisotopic technique. Scans were done 24 hours after technetium-99m administration (n = 30). In 9 patients a dynamic scintigraphy was performed immediately after colloid administration, and samples of blood and tracheal and oropharyngeal secretions were obtained basally, 30 minutes, and 24 hours after technetium administration and analyzed for radioactivity using a gamma counter. RESULTS: Both groups were similar in age, underlying diagnosis, number of days of mechanical ventilation at the day of study, and mortality. There were no GER reaching the oropharynx and aspiration of gastric contents in both groups. CONCLUSIONS: GER and aspiration of gastric contents were not detected in MV patients using small-bore NGTs and may be a simple measure to prevent ventilator-associated pneumonia.

[An alternative method to determine the radiochemical purity of the 99mTC-tetrofosmine preparations]. / Un método alternativo para determinar la pureza radioquímica de las preparaciones de 99mTc-Tetrofosmina.

This paper describes a new quality control method to determine the radiochemical purity (RCP) value of Technetium-99m-Tetrofosmin preparations. The results of this procedure were compared with the results obtained with the method suggested by the manufacturer of the kit (classic method), consisting in thin-layer chromatography involving the use of a single strip of ITLC/SG as the stationary phase, and a acetone:dichlorometane 35:65 (Ac:DCM) solvent mixture as the mobile phase. The method that is proposed in this paper (alternative method) uses the same stationary phase but it is developed in a single solvent, methylethylketone (MEK). This method has the following advantages: a better capacity to separate the 99mTc-Tetrofosmin complex from 99mTcO4- and 99mTcO2 impurities, a faster chromatographic developing time and the use of a single solvent in the quality control.

Persistence of Cajal-Retzius cells in the adult human cerebral cortex. An immunohistochemical study.

The presence of Cajal-Retzius cells in the adult human prefrontal and visual cortices has been demonstrated with calcium binding protein immunocytochemistry and NADPH-diaphorase histochemistry. These cells expressed parvalbumin, calbindin and calretinin calcium binding proteins and displayed NADPH-diaphorase enzyme activity. The three basic morphological profiles-horizontal, pyriform and multipolar-were observed. The morphologies of labelled cells resembled those of neurons observed in Golgi studies of the human cerebral cortex. The presence of calcium binding proteins and NADPH-diaphorase in these cells suggests a possible inhibitory role as GABAergic neurons. The persistence of Cajal-Retzius cells in the adult cerebral cortex supports the idea that they undergo developmental dilution rather than postnatal degeneration.

Differential regional and cellular distribution of dopamine D2-like receptors: an immunocytochemical study of subtype-specific antibodies in rat and human brain.

Dopamine D2-like receptors (D2, D3, and D4) are major targets for action of typical and atypical neuroleptics, commonly used in the treatment of schizophrenia. To understand their individual functional contribution, subtype-selective anti-peptide antibodies were raised against D2, D3, and D4 receptor proteins. The antibodies were shown to be specific on immunoblots of rat brain membranes and immunoprecipitated the solubilized native dopamine receptors in an antibody concentration-dependent manner. In addition, they also bind selectively to the respective recombinant D2, D3, and D4 receptor membrane proteins from cDNA transfected cells. Immunolocalization studies show that the D2-like receptor proteins had differential regional and cellular distribution in the cerebral cortex, hippocampus, basal ganglia, cerebellum, and midbrain, thus providing anatomical substrate for area-specific regulation of the dopamine neurotransmission. In cortical neurons, D4 receptor protein was found in both pyramidal and nonpyramidal cells, whereas D2 and D3 seem to be mostly associated with nonpyramidal interneurons. In rat hippocampus, the expression pattern of D2-like receptors (D4>D3>D2) mirrored that obtained with immunoprecipitation studies. D2 and D4 receptor immunolabeling was observed in the thalamic reticular nucleus, which was negative for the D3 subtype. Species differences were also observed; for example, the D4 subtype receptor is the most highly expressed protein in the rat cortex, whereas it is significantly less in human cortex. Differential patterns of D2, D3, and D4 receptor expression in rat and human brain should shed light on the therapeutic actions of neuroleptic drugs and may lead to the development of more specifically targeted antipsychotic drugs.

A tangential neuronal migration in the olfactory bulbs of adult lizards.

Tritiated thymidine ([3H]thymidine) autoradiography at different times after experiments showed that postnatally generated neurones in the adult lizard olfactory bulbs are not generated in a local germinative zone but in the ventricular zone (VZ) of the cerebral hemispheres, which is a long distance from the olfactory bulbs. The new cells originating in the VZ of rostral telencephalon migrate to both main and accessory olfactory bulbs through the olfactory peduncle, along a highly restricted pathway orthogonal to the orientation of radial glial fibres. Our results suggest that the olfactory bulb interneurones of adult lizards may follow a tangential migration route from their germinative zone, as is the case in mammals.

Gastroesophageal reflux in intubated patients receiving enteral nutrition: effect of supine and semirecumbent positions.

The incidence of gastroesophageal reflux (GER) in critically ill patients as well as the effect of a nasogastric tube (NGT) and body position as risk factors for GER were determined. Seventy patients with orotracheal intubation receiving enteral nutrition through a NGT for more than 48 hours were prospectively studied with two randomly assigned body positions: supine or semirecumbent. Detection of GER was achieved by scintigraphy after labeling gastric contents with 500 microCi of technetium-99m sulfur colloid administered through the NGT. In 50 patients scintigraphy was performed after subjects had remained in the randomized position for 2 hours with the NGT pinched. Twenty additional patients were studied after the NGT had been removed. In 50 patients with NGT, GER was present in 74% (37 of 50) and was higher in the supine position (81%, 21 of 26) than in the semirecumbent position (67%, 16 of 24), but this difference was not statistically significant (p = .26). In 20 patients without NGT, the incidence of GER was 35% (7 of 20) and it was also higher in the supine (50%, 6 of 12) than in the semirecumbent position (12%, 1 of 8, p = .16). There was a statistically significant difference between GER in patients with and without NGT (74% vs 35%, p = .0002). These data show that there is a high incidence of GER in patients with orotracheal intubation and NGT. The presence of a NGT is a risk factor for GER. Semirecumbency does not prevent GER, but there is less incidence than in the supine position.

Clinical comparison of 99mTc-HMDP and 99mTc-MDP. A multicenter study.

99mTc-Hydroxymethylene diphosphonate (HMDP) was compared to 99mTc-methylene diphosphonate (MDP) with respect to image quality, lesion detectability, and the uptake ratios of normal bone to soft tissue (B/S), metastatic bone to soft tissue (M/S) and bone metastases to normal bone (M/B) at 2 and 3 h after injection in the same subjects. Thirty-three patients with bone metastases were examined in six nuclear-medicine departments, with each center using its usual bone-scanning protocol which was identical for both compounds in the same patient. The uptake of 99mTc-HMDP in normal bone (B/S) was significantly higher than that of MDP at 2 and 3 h, but there were no significant differences between the two compounds with regard to the M/S or M/B ratios. The M/B of HMDP at 2 h was not significantly different from that of MDP at 3 h, the latter showing a significantly higher B/S and M/S ratio. All lesions were detected with both compounds, even at 2 h. The image quality was rated as follows (in decreasing order): HMDP (3 h), MDP (3 h), HMDP (2 h), and MDP (2 h). HMDP was shown to be a useful bone-imaging agent, especially when shorter intervals between injection and recording are required.