The influence of age on neurotransmitter turnover in the rat's superior colliculus.

Measurements of the turnover of dopamine, noradrenaline and serotonin and their metabolites have been performed in the superior colliculus of adult and aged rats. The turnover of dopamine, noradrenaline and their metabolites after pargyline treatment was significantly lower in aged rats than in adults. On the contrary, the synthesis rate of serotonin (measured by accumulation of 5-hydroxytryptophan after decarboxylase blockade) and the turnover rate of serotonin (after pargyline treatment) did not change during aging. These findings suggest that aging has a different effect on catecholamines and serotonin turnover in the superior colliculus of the aged rats.     

Rate of flow of digesta and electrical activity of the small intestine in dogs and sheep.

1. Spiking activity of the small intestine in the conscious dog and sheep was recorded continuously from electrodes chronically implanted on the jejunum and summed at intervals of 20 sec. The activity was related to the transit time and flow rate of intestinal contents as estimated by phenol red and by dilution of continuous marker infusions respectively. Also in some sheep the flow of digesta was measured directly from a cannula in the proximal part of the jejunum, and also by use of an electromagnetic flow meter. 2. In the fasted dog and in sheep on a normal diet the intestinal activity was characterized by a migrating myo-electric complex comprising an irregular phase followed by a regular phase. These migrating myo-electric complexes occurred regularly after a period of inactivity at a frequency of 15-20/24 hr. In dogs after feeding, a continuous spiking activity appeared and persisted for periods of 7-8 hr. This was associated with much higher rates of flow and shorter transit times than were observed during fasting. In sheep, continuous spiking activity could be induced by intravenous injection of 5-hydroxytryptophan and this, similarly, was accompanied by a more rapid flow and a shorter transit time than recorded during the control period. 3. In both species the longest transit time occurred when a phenol red bolus was injected during the period of electrical inactivity. Relatively short transit times were observed when the bolus was administered just before the period of regular spiking activity. 4. When relaxation of the bowel was induced by intraperitoneal injection of hypertonic saline there was no spiking activity and the transit time for the infused solution was greatly lengthened, especially in the sheep. A noticeable flow of digestive contents persisted in the dog. 5. In the sheep the intestinal contents flowed intermittently during periods of 10-15 min and at the same frequency as the migrating myo-electric complex. Two thirds of this flow took place in the 4-6 min immediately preceding the periods of irregular spiking activity. 6. It is concluded that in the fasted dog and in the sheep the migrating myo-electric complex controls the pressure gradients on which the flow of intestinal contents depends. This is accomplished in the main by the prolonged phase of irregular spiking activity, and it is suggested that the regular spiking activity which follows it, though not in itself propulsive, serves as a barrier to prevent backflow of digesta into the quiescent part of the intestine. When continuous spiking activity is induced, by feeding in the dog and by injection of 5-hydroxytryptophan in the sheep, no part of the intestine is quiescent and the transit time is shortened by the incessant irregular spiking activity.     

Increased Bronchial Hypersensitivity after Early and Late Bronchial Reactions Provoked by Allergen Inhalation

The non-specific bronchial reactivity following bronchial allergen challenge was studied in 40 patients with allergic bronchial asthma, particularly in subjects without definite late reactions 6 h after the provocations (reduction in peak expiratory flow or forced expiratory volume in 1 s of less than 15% of the control value at this time). Among a group of 21 patients submitted to bronchial provocation tests, 13 carried out maximal exercise tests 6 and 1 week after the allergen challenge. In another group of 19 patients, the bronchial hyperreactivity to methacholine was assessed before and 6 h and 1 week after challenge. Two patients with a dual response (early & late) reacted with bronchial obstruction to the exercise. Exercise tests performed after 1 week did not provoke asthma in any patient. In the methacholine group a marked increase in responsiveness to methacholine 6 h after the provocation was observed in those patients with a dual response who were tested and in those with equivocal late reactions and even in three patients with an isolated immediate reaction. The increases responsiveness was still present in many patients 1 week after challenge. The airway caliber did not influence the degree of responsiveness to methacholine. Nor did the degree of responsiveness have any influence on the patterns of reactions observed after allergen exposure. It was concluded that in some individuals exposure to the relevant allergen predisposes them to exercise-inducible bronchial obstruction. Further, it was confirmed that non-specific bronchial reactivity can be increased not only in patients with late responses - both definite and equivocal--but also in some patients with immediate reactions alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intracellular lectin-binding sites in symbiont-bearingCrithidia species

Crithidia oncopelti, C. deanei, andC. desouzai are flagellates of the Trypanosomatidae family that present bacterium-like endosymbionts in their cytoplasm. Direct and indirect lectin-gold labeling techniques were used at the electron microscopic level in Lowicryl K4M-embedded cells to demonstrate the presence of intracellular lectin-binding sites. We used the lectinsUlex europaeus I, Griffonia simplicifolia II, Ricinus communis I, Arachis hypogaea, G. simplicifolia I, Wistaria floribunda, Limulus polyphemus, andCanavalia ensiformis, which recognize -l-fucose, - and -N-acetylglucosamine, -galactose and -N-acetylgalactosamine, -galactose, -galactose, -N-acetylgalactosamine, sialic acid and -d-mannose, and -d-glucose residues, respectively. The nucleus was the cellular structure most frequently labeled by the lectins. The Golgi complex was seldom labeled, whereas the endoplasmic reticulum and the flagellar pocket presented a large number of binding sites. Symbionts had their two unit membranes weakly labeled by the different lectins but displayed no labeling of the space between the membranes.     

Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia

BACKGROUND: Most patients with familial primary pulmonary hypertension have defects in the gene for bone morphogenetic protein receptor II (BMPR2), a member of the transforming growth factor beta (TGF-beta) superfamily of receptors. Because patients with hereditary hemorrhagic telangiectasia may have lung disease that is indistinguishable from primary pulmonary hypertension, we investigated the genetic basis of lung disease in these patients. METHODS: We evaluated members of five kindreds plus one individual patient with hereditary hemorrhagic telangiectasia and identified 10 cases of pulmonary hypertension. In the two largest families, we used microsatellite markers to test for linkage to genes encoding TGF-beta-receptor proteins, including endoglin and activin-receptor-like kinase 1 (ALK1), and BMPR2. In subjects with hereditary hemorrhagic telangiectasia and pulmonary hypertension, we also scanned ALK1 and BMPR2 for mutations. RESULTS: We identified suggestive linkage of pulmonary hypertension with hereditary hemorrhagic telangiectasia on chromosome 12q13, a region that includes ALK1. We identified amino acid changes in activin-receptor-like kinase 1 that were inherited in subjects who had a disorder with clinical and histologic features indistinguishable from those of primary pulmonary hypertension. Immunohistochemical analysis in four subjects and one control showed pulmonary vascular endothelial expression of activin-receptor-like kinase 1 in normal and diseased pulmonary arteries. CONCLUSIONS: Pulmonary hypertension in association with hereditary hemorrhagic telangiectasia can involve mutations in ALK1. These mutations are associated with diverse effects, including the vascular dilatation characteristic of hereditary hemorrhagic telangiectasia and the occlusion of small pulmonary arteries that is typical of primary pulmonary hypertension.     

Nitric oxide mediates the inhibition of neutrophil migration induced by systemic administration of LPS

To investigate the role of NO in the inhibition of neutrophil migration by circulating endotoxin, mice were pretreated with NO synthase inhibitors or with a free radical scavenger (D-penicillamine), before intravenous LPS injection. LPS dose-dependently inhibited the thioglycollate-induced neutrophil migration into the peritoneal cavities. Aminoguanidine, a selective inducible NO synthase inhibitor, abolished the inhibition of neutrophil migration and the increase in serum nitrate levels induced by a nonlethal dose of LPS. During lethal endotoxemia aminoguanidine partially abolished the neutrophil migration inhibition. Additionally, D-penicillamine prevented the inhibition of neutrophil migration caused by LPS. However, Nitro-L-Arginine, a selective constitutive NO synthase inhibitor, did not prevent neutrophil migration inhibition. Aminoguanidine treatment did not affect the systemic increased levels of TNF-, IL-1, and IL-10, suggesting that NO is the final mediator involved in the inhibition of neutrophil migration. Our results suggest that NO released by the inducible NO synthase mediates the inhibition of neutrophil migration mediated by circulating LPS.     

Fluconazole induces genotoxicity in cultured human peripheral blood mononuclear cells via immunomodulation of TNF-α, IL-6, and IL-10: new challenges for safe therapeutic regimens

Context: Fluconazole (FNZ) is a drug used in antifungal therapy. However, the minimum FNZ dose to interfering with immune responses or inducing DNA damage is still unknown.

Objective: This study investigated the toxicological profile of FNZ on cultured human peripheral blood mononuclear cells (PBMCs) treated with different concentrations of this azole.

Materials and methods: Cultured PBMCs were exposed to FNZ (6, 12, 30, 60 and 120?μg/mL) and the toxicological profile was assessed by the following parameters: cytotoxic and nuclear division index (necrotic, apoptotic and viable cells), DNA damage (alkaline comet test), mutagenic potential (micronucleus test), cytokine modulation (IL-1, IL-6, IL-10, TNF-α, IFN-γ), and predictive toxicity (Osiris^® and LAZAR^® programs).

Results: Our results demonstrated that FNZ induced cellular DNA damage and mutagenicity at concentrations above the plasma peak (>30?μg/mL) and 6?μg/mL, respectively, which was associated with increased TNF-α, and decrease IL-6 and IL-10 concentrations. These effects may be related to increased apoptosis and cytotoxic nuclear division index in the cultured PBMCs. In silico results indicated potential mutagenic, tumorigenic, irritant, and carcinogenic effects, which were partially confirmed by the above assays.

Discussion and conclusions: Together, these findings suggest the need to rationalize the use of FNZ, especially if it is used for long periods or with concomitant pathologies requiring azole therapy that may increase FNZ's plasma concentration.     

Age-related changes of catecholamines and their metabolites content in the visual system of the rat

The changes in the content of the catecholamines in each structure of the geniculate and extrageniculate visual system of the rat during the aging period (6-30 months) have been studied. Dopamine was found at lower levels than noradrenaline in all the structures. The dopamine and noradrenaline showed different developmental profiles. Dopamine and its metabolite levels decreased in the lateral geniculate and visual cortex and increased in superior colliculus and posterior thalamus. Noradrenaline and its metabolites increased in all structures during the aging period. However, 3-methoxy-4-hydroxyphenylglycol/noradrenaline and normetanephrine/noradrenaline ratios decreased in all structures except in superior colliculus. These results suggest age-related changes in the catecholamines in the visual system of the rat.     

Cesarean Delivery and Risk of Excess Weight Among Brazilian Preschool Children

Maternal and Child Health Journal - To study the relationship between cesarean Delivery (CD) and overweight in preschool children, considering the presence of birth aspects and demographic...     

Association Between Maternal Work and Exclusive Breastfeeding in Countries of Latin America and Caribbean

Maternal and Child Health Journal - The aim of this study was to estimate the association between individual and contextual characteristics related to maternal work and exclusive breastfeeding...