Intranasal Administration of the Dopaminergic Agonists l-DOPA, Amphetamine, and Cocaine Increases Dopamine Activity in the Neostriatum: A Microdialysis Study in the Rat

Abstract: The effectiveness of intranasal drug administration to stimulate central neuronal systems is well known from drug addiction and has also been considered as an alternative pharmacokinetic approach to treat brain disorders such as Parkinson's disease. In the present study, the possible neurochemical effects of intranasal administration of the psychostimulants cocaine and amphetamine and of the antiparkinsonian drug l -DOPA were analyzed. By using in vivo microdialysis in the urethane-anesthetized rat, it was found that unilateral intranasal administration of either of the psychostimulants led to huge and rapid increases of extracellular dopamine levels in the neostriatum followed by decreases of its metabolites dihydroxyphenylacetic acid and homovanillic acid. Furthermore, intranasal administration of l -DOPA, but not of the saline vehicle, also led to increased extracellular levels of neostriatal dopamine and to increases of its metabolites. Because the effect of intranasal l -DOPA on neostriatal dopamine was observed only ipsilaterally but not contralaterally to the side of intranasal drug administration, it can be hypothesized that l -DOPA was not effective via passage through the circulation but may have acted through a neuronal or an extraneuronal route. These data provide neurochemical evidence that the intranasal route may not only be efficient in drug abuse, but may also be useful to target the brain therapeutically, as in the case of neurodegenerative brain disorders.     

Proteomic analysis of kidney in rats chronically exposed to fluoride

Two-dimensional gel electrophoresis (2-DE) was used to better understand alterations in renal metabolism induced by fluoride (F). Three groups of weanling male Wistar rats were treated with drinking water containing 0 (control), 5, or 50 ppm F for 60 days (n = 6/group). Kidneys were collected for proteomic and histological (HE) analysis. After protein isolation, renal proteome profiles were examined using 2-DE and Colloidal Coomassie Blue staining. Protein spots with a 2-fold significant difference as detected by quantitative intensity analysis (Image Master Platinum software) and t-test (p < 0.05) were excised and analyzed by MALDI-TOF MS (matrix assisted laser desorption ionization-time-of-flight mass spectrometry). The histological analysis revealed no damage in kidneys induced by F, except for a vascular congestion in the 50 ppm F group. Between control vs 50 ppm F, and control vs 5 ppm F groups, 12 and 6 differentially expressed proteins were detected, respectively. Six proteins, mainly related with metabolism, detoxification and housekeeping, were successfully identified. At the high F group, pyruvate carboxylase, a protein involved in the formation of oxaloacetate was found to be downregulated, while enoyl coenzyme A hydratase, involved in fatty acids oxidation, was found to be upregulated. Thus, proteomic analysis can provide new insights into the alterations in renal metabolism after F exposure, even in low doses.     

Enkephalin- and serotonin-like immunoreactivity in the aortico-pulmonary paraganglia of the white-belly opossumDidelphis albiventris (Marsupialia)

Summary Serial histological sections of the interatrial septum and basal heart vessels of the weaned and juvenile white-belly opossum (Didelphis albiventris) were obtained in order to study the presence of paraganglia and their content of regulatory peptides and serotonin. Paraganglion groups were mapped between the aorta and pulmonary arteries and close to the bifurcation of the pulmonary trunk and were found to contain cells with immunoreactivity to serotonin and to the neuroendocrine markers PGP 9.5 and NSE. When these paraganglia were tested for immunoreactivity to a battery of regulatory peptides, all were found to be positive for methionin-enkephalin, leucine-enkephalin and galanin. The hypothesis is raised that these peptides and serotonin, besides catecholamines, produced by these paraganglia may play a physiological role in the functions of the cardiovascular system of the white-belly opossum.Work supported by grants from FINEP and CNPq (Brazil).     

Stress exposure in specific growth periods associates with children's weight,height, and body mass index

Objectives

We investigate associations between children exposure to stressful events, considering: (1) the period in which the event took place, (2) the type of event, and (3) the cumulative effect of the events on children's weight, height and body mass index (BMI).

Methods

A total of 8429 Portuguese children (3349 exposed to at least one stressful event during their lifetime; 50.2% males; mean age = 7.21 ± 1.85 years) were included in the analysis. The occurrence of stressful (i.e., adverse) events was reported in a parental questionnaire; children's weight and height were objectively measured.

Results

When the stress event took place in the first 2 years of life, compared with during pregnancy or after the 2 years, children were shorter; but the association was weak and only significant for boys. After adjustment for child's birthweight, gestational age, breastfeeding duration, number of siblings, and father's education, the experience of 3+ stressful events (vs. 1 or 2) was associated with higher weight and height in boys. No interaction effect was found between stress and BMI.

Discussion

We found some evidence of associations between exposure to stressful events and physical growth of boys. We highlight the complex relationship between exposure to stressful experiences and children's physical growth, particularly the different effects of specific characteristics of the stress event and the sex differences.

     

Virological study of a dengue type 1 epidemic at Rio de Janeiro

A dengue outbreak started in March, 1986 in Rio de Janeiro and spread very rapidly to other parts of the country. The great majority of cases presented classical dengue fever but there was one fatal case, confirmed by virus isolation. Dengue type 1 strains were isolated from patients and vectors (Aedes aegypti) in the area by cultivation in A. albopictus C6/36 cell line. The cytopathic effect (CPE) was studied by electron microscopy. An IgM capture test (MAC-ELISA) was applied with clear and reproducible results for diagnosis and evaluation of virus circulation; IgM antibodies appeared soon after start of clinical disease, and persisted for about 90 days in most patients. The test was type-specific in about 50% of the patients but high levels of heterologous response for type 3 were observed. An overall isolation rate of 46.8% (813 virus strains out of 1734 specimens) was recorded. The IgM test increased the number of confirmed cases to 58.2% (1479 out of 2451 suspected cases). The importance of laboratory diagnosis in all regions where the vectors are present is emphasized.     

Identification of receptors for prothymosin alpha on human lymphocytes.

Prothymosin alpha (ProTalpha) is a highly conserved and widely distributed protein whose physiological functions remain elusive. In previous work we identified high and low affinity-binding sites for ProTalpha in lymphoid cells. Here we demonstrate, by affinity cross-linking and affinity chromatography, the existence of three binding partners (31, 29, and 19 kDa) for ProTalpha in the membrane of PHA-activated lymphoblasts. These surface molecules possess the expected affinity and specificity for a ProTalpha receptor. Examination of the expression of this complex of molecules by flow cytometry reveals that they bind ProTalpha in a specific and saturable way. In addition, the distribution of the receptor on the cell surface was studied by fluorescence microscopy; a cap-like structure at one of the poles of the cells was identified. These results represent a new and promising approach in the research on ProTalpha, opening the way toward the understanding of the molecular mechanism of action of this protein.     

Scanning electron microscopy of the dorsal vessel of Panstrongylus megistus (Burmeister, 1835) (Hemiptera: Reduviidae).

In this study we analyzed the microanatomy of the dorsal vessel of the triatomine Panstrongylus megistus. The organ is a tubule anatomically divided into an anterior aorta and a posterior heart, connected to the body wall through 8 pairs of alary muscles. The heart is divided in 3 chambers by means of 2 pairs of cardiac valves. A pair of ostia can be observed in the lateral wall of each chamber. A bundle of nerve fibers was found outside the organ, running dorsally along its major axis. A group of longitudinal muscular fibers was found in the ventral portion of the vessel. The vessel was found to be lined both internally and externally by pericardial cells covered by a thin laminar membrane. Inside the vessel the pericardial cells were disposed in layers and on the outside they formed clusters or rows.     

About photo-damage of human hair.

This paper reviews the current knowledge about human hair photodamage and the photodegradation mechanisms proposed in the literature. It is shown that there are still a number of questions without answer regarding this issue. For example, a better understanding of the hair structural changes caused by different radiation wavelengths is still lacking. We also find controversies about the effects of sun exposure on different hair types. Explanations to these questions are frequently sustained on the amount and type of melanin of each hair, but factors such as the absence of knowledge of melanin structure and of established methodologies to use in human hair studies make it difficult to reach a general agreement on these issues.