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Biomedical subjects

S Mora

Publications and source records attributed to S Mora.

At least 19 recordsLinked to original sources

The hydroalcoholic extract of Salvia elegans induces anxiolytic- and antidepressant-like effects in rats.

Behavioral effects of a hydroalcoholic (60% ethanol) extract from the leaves of Salvia elegans Vahl (Lamiaceae) were studied in male Sprague-Dawley rats. The extract was administered intraperitoneally and its effects on spontaneous motor activity (total motility, locomotion, rearing and grooming behavior) were monitored. Putative anxiolytic and antidepressant properties of Salvia elegans were studied in the elevated plus-maze test (EPM) and in the forced swimming test (FST), respectively. Deleterious effects of Salvia elegans on learning and memory were also studied by using active and passive avoidance paradigms. The results revealed that all doses (3.12, 12.5, 25 and 50 mg/kg) of the extract caused a significant decrease in total motility, locomotion, rearing and grooming behavior. Only the dose of 12.5 mg/kg increased the exploration of the EPM open arms in a similar way to that of diazepam (1 mg/kg). In the FST, all doses of the extract induced a reduction of immobility, in a similar way to that of fluoxetine (10 mg/kg) and imipramine (12.5 mg/kg), along with a significant increase in the time spent in swimming behavior. Acquisition of active avoidance responses was disrupted by pre-treatment with the extract, but retention of a passive avoidance response was not significantly modified. These results suggest that some of the components of the hydroalcoholic extract of Salvia elegans have psychotropic properties, which deserve further investigation.

Animals↗

Antibodies to recombinant human tissue-transglutaminase in coeliac disease: diagnostic effectiveness and decline pattern after gluten-free diet.

BACKGROUND/AIMS: To assess the sensitivity and specificity of IgA and IgG tissue-transglutaminase antibodies assay, the pattern of antibody decline after gluten withdrawal and their modifications with reference to dietary compliance. SUBJECTS: We studied sera from 143 untreated coeliac children and adolescents (8.8+/-6.1 years), 212 sera from 97 of those patients after gluten withdrawal, and 64 control subjects with non-coeliac intestinal disorders (6.8+/-4.8 years). METHODS: Samples were tested for IgA and IgG class tissue-transglutaminase antibodies by radiobinding assay, using human-derived tissue-transglutaminase, and for IgA anti-endomysium antibodies by indirect immunofluorescence on monkey oesophagus. RESULTS: Untreated coeliac patients had significantly higher titres of IgA and IgG tissue-transglutaminase antibodies than controls (p<0.00001); the diagnostic sensitivity was 95.8% and 99.3%, respectively, and the specificity was 95.3%. Three patients with selective IgA deficiency were positive for IgG tissue-transglutaminase antibodies. The concordance rate between IgA tissue-transglutaminase antibodies and anti-endomysium antibodies was 98.1%. Patients on gluten-free diet showed a significant decrease in IgA and IgG tissue-transglutaminase antibodies with respect to untreated patients (p<0.0001). Tissue-transglutaminase was more sensible than anti-endomysium antibodies to detect small amounts of gluten intake when the compliance was poor. CONCLUSIONS: The recombinant human tissue-transglutaminase antibodies assay is a highly sensitive and specific test for diagnosis of coeliac disease, and it is useful in monitoring the compliance to gluten-free diet.

Celiac Disease↗

The anxiolytic-like effects of Aloysia polystachya (Griseb.) Moldenke (Verbenaceae) in mice.

The aim of the present work is to demonstrate the putative sedative and anxiolytic-like effects of a hydro-ethanolic extract obtained from the aerial parts of Aloysia polystachya (Verbenaceae) in male mice using several behavioural assays. Groups of male mice orally treated with doses of 1.0, 10.0 and 100.0 mg/kg of the extract did not show any significant alteration of their locomotor activity, body temperature or motor coordination. The same treatment increased the duration of the sleeping time induced by 30.0 mg/kg i.p. of sodium pentobarbital. However, the sleeping time induced by ethyl ether was not modified by the oral administration of the extract, not confirming the putative sedative effect of the plant. The ethanolic extract also significantly increased the percentage of both entries (1.0 and 100.0 mg/kg) and the time spent (10.0 and 100.0 mg/kg) into the open arms of the elevated plus maze (EPM). Nevertheless, the binding of (3)H-flunitrazepam ((3)H-FNZ) to the benzodiazepine binding site (BDZ-bs), in washed crude synaptosomal membranes from rat cerebral cortex, was not affected by the semi-purified components from Aloysia polystachya. These results indicate an anxiolytic-like profile of action for the extract of Aloysia polystachya without sedative side effect, being this activity probably mediated by other mechanism than BDZ-bs modulation at the GABA(A) receptors.

Animals↗

Anxiolytic and antidepressant-like effects of the hydroalcoholic extract from Aloysia polystachya in rats.

Behavioral effects of a hydroalcoholic extract from leaves of Aloysia polystachya (Griseb.) Moldenke (Verbenaceae) were studied in female Sprague-Dawley rats. The extract was administered intraperitoneally and its effects on spontaneous motor activity (total motility, locomotion, rearing and grooming behavior) were monitored. Anxiolytic-like properties were studied in the elevated plus-maze (EPM) test and the possible antidepressant-like actions were evaluated in the forced swimming test (FST). The results revealed that high doses of the extract (25 and 50 mg/kg, i.p.) caused a significant decrease in total motility, locomotion, rearing and grooming behavior. All doses injected (from 1.56 to 50 mg/kg) increased the exploration of the EPM open arms in a similar way to that of diazepam (1 mg/kg, i.p.). In the FST, the extract (12.5, 25 and 50 mg/kg) was as effective as fluoxetine (10 mg/kg, i.p.) and imipramine (12.5 mg/kg, i.p.) in reducing immobility, along with a significant increase in swimming and climbing, respectively. These results suggest that some of the components of the hydroalcoholic extract of A. polystachya, such as thujone and carvone among others, may have sedative, anxiolytic and antidepressant-like properties which deserve further investigation.

Animals↗

Chronic stress impairs acoustic conditioning more than visual conditioning in rats: morphological and behavioural evidence.

Chronic stress affects brain areas involved in learning and emotional responses. These alterations have been related with the development of cognitive deficits in major depression. The aim of this study was to determine the effect of chronic immobilization stress on the auditory and visual mesencephalic regions in the rat brain. We analyzed in Golgi preparations whether stress impairs the neuronal morphology of the inferior (auditory processing) and superior colliculi (visual processing). Afterward, we examined the effect of stress on acoustic and visual conditioning using an avoidance conditioning test. We found that stress induced dendritic atrophy in inferior colliculus neurons and did not affect neuronal morphology in the superior colliculus. Furthermore, stressed rats showed a stronger impairment in acoustic conditioning than in visual conditioning. Fifteen days post-stress the inferior colliculus neurons completely restored their dendritic structure, showing a high level of neural plasticity that is correlated with an improvement in acoustic learning. These results suggest that chronic stress has more deleterious effects in the subcortical auditory system than in the visual system and may affect the aversive system and fear-like behaviors. Our study opens a new approach to understand the pathophysiology of stress and stress-related disorders such as major depression.

Acoustic Stimulation↗

Structuring sedimentation in a shear-thinning fluid.

We study the sedimentation of suspensions of monodisperse non-Brownian particles in a shear-thinning polymeric fluid. We observe the formation of particle-rich structures and show that they are associated with a well-defined flow pattern. The results suggest that the observed structuring is a consequence of particle aggregation that amplifies concentration heterogeneities, the flow pattern being further driven by a gravitational instability.

Journal Article↗

Structure and fluctuations of a single floating lipid bilayer.

A single lipid molecular bilayer of 17 or 18 carbon chain phosphocholines, floating in water near a flat wall, is prepared in the bilayer gel phase and then heated to the fluid phase. Its structure (electron density profile) and height fluctuations are determined by using x-ray reflectivity and non-specular scattering. By fitting the off-specular signal to that calculated for a two-dimensional membrane using a Helfrich Hamiltonian, we determine the three main physical quantities that govern the bilayer height fluctuations: The wall attraction potential is unexpectedly low; the surface tension, roughly independent on chain length and temperature, is moderate (approximately 5 x 10(-4) J.m(-2)) but large enough to dominate the intermediate range of the fluctuation spectrum; and the bending modulus abruptly decreases by an order-of-magnitude from 10(-18) J to 10(-19) J at the bilayer gel-to-fluid transition.

Electrons↗

Analysis of bone mineral content in horizontally HIV-infected children naïve to antiretroviral treatment.

Low bone mass is a frequent finding in HIV-infected individuals. Reduced bone mass has been found in vertically infected children who are receiving antiretroviral treatment. Little is known about bone mass in horizontally infected young patients who are naïve to antiretroviral therapy. We measured the bone mineral content (BMC) at the lumbar spine and in the whole skeleton by using dual-energy X-ray absorptiometry (DXA) in 16 HIV-infected children (age 9.3 +/- 3.9 years) naïve to antiretroviral treatment, and in 119 healthy children (age 9.7 +/- 3.3 years). Thirteen patients were also pair-matched by anthropometric measures, sex, and age with healthy children. Median spine BMC of HIV-infected children was 14.9 g (8.2-39.2 g), and whole body BMC was 1106.1 g (55.5-2344.1 g). Spine BMC of healthy children was 18.6 g (6.8-52.2 g), and whole body BMC was 1213.5 g (541.0-2722.0 g). Multivariate analysis showed a mean difference of spine BMC values of 0.004 g (P = 0.64) between the two groups. Similarly, the whole body BMC difference between the two groups (0.001 g) was not statistically significant (P = 0.55). Mean spine BMC measurements in the case-control evaluation were 21.1 g (9.7 g) (patients), and 22.3 g (6.9 g) (controls). Whole body BMC measurements of patients and controls were 1258.5 g (539.6 g) and 1311.1 g (479.2 g), respectively. In both cases the differences were not significant. The duration of HIV infection did not relate to BMC values. In conclusion, horizontally HIV-infected children naïve to antiretroviral therapy have bone mineral measurements comparable to those of healthy children.

Absorptiometry, Photon↗

Central nervous system activity of the hydroalcoholic extract of Casimiroa edulis in rats and mice.

In order to evaluate the effects produced by the hydroalcoholic extract of leaves from Casimiroa edulis on the central nervous system, different behavioral tests and animal models of depression and anxiety were performed. The extract was administered intraperitoneally in male and female rats and tested on spontaneous motor activity, locomotor activity, exploration of an elevated plus-maze (EPM) and in the forced swimming test (FST). In addition, the extract was administered orally in male and female mice and evaluated in the following tests: general observation, pentobarbital-induced hypnosis, EPM, rota-rod, hole-board, and marble-burying. The results revealed that, in rats, the extract caused considerable reduction of locomotor and exploratory activities and increased the exploration of the EPM open arms in a similar way that diazepam. In the FST, the extract was as effective as fluoxetine in inducing shortening of immobility, along with a significant increase on climbing duration. On the other hand, in mice, the extract prolonged pentobarbital-induced hypnosis, increased exploration of the EPM open arms and partially protected from the pentylenetetrazol-induced convulsions. No significant effect was evident on motor coordination, hole-board and marble-burying tests. These results suggest that the hydroalcoholic extract of Casimiroa edulis may contain sedative principles with potential anxiolytic and antidepressant properties, which need further investigation.

Administration, Oral↗

Inhibition of DT-diaphorase potentiates the in vivo neurotoxic effect of intranigral injection of salsolinol in rats.

The present study shows that intranigral injection of dicoumarol, a DT-diaphorase inhibitor, potentiates the neurotoxic effect of salsolinol (salsolinol 1.25 nmoles plus dicoumarol 2 nmoles; in 2 microl). Rats treated with dicoumarol plus salsolinol presented a characteristic contralateral rotational behaviour when they were stimulated with apomorphine (0.5 mg/kg, s.c.), similar to rats injected unilaterally with 6-hydroxydopamine (6-OHDA). These rats also exhibited impairment of motor and cognitive behaviours. The results support the hypothesis that DT-diaphorase plays a protective role in the nigrostriatal dopaminergic systems.

Animals↗

X-ray synchrotron study of liquid-vapor interfaces at short length scales: effect of long-range forces and bending energies.

We have investigated the small-scale structure of the liquid-vapor interface using synchrotron x-ray scattering for liquids with different molecular structures and interactions. The effective momentum-dependent surface energy first decreases from its macroscopic value due to the effect of long-range forces, and then increases with increasing wave vector. The results are analyzed using a recent density functional theory. The large wave-vector increase is attributed to a bending energy for which local and nonlocal contributions are equally important.

Journal Article↗

Behavioral effects of aminochrome and dopachrome injected in the rat substantia nigra.

The exact mechanism of cell death in neurodegenerative diseases remains obscure, although there is evidence that their pathogenesis may involve the formation of free radicals originating from the oxidative metabolism of catecholamines. The purpose of this study was to evaluate the degree of neurodegenerative changes and behavioral impairments induced by unilateral injection into the rat substantia nigra of cyclized o-quinones, aminochrome and dopachrome, derived from oxidizing dopamine and L-DOPA, respectively, with Mn(3+)-pyrophosphate complex. The behavioral changes were compared with those induced after selective lesions of dopaminergic neurons with 6-hydroxydopamine (6-OHDA). Intranigral injection of aminochrome and dopachrome produced impairment in motor and cognitive behaviors. The behavioral impairment was also revealed by apomorphine-induced rotational asymmetry. Apomorphine (0.5 mg/kg sc) significantly increased rotational behavior in rats injected with aminochrome and dopachrome. These rats presented a clear motor bias showing a significant contralateral rotation activity, similar but less vigorous that in rats injected with 6-OHDA. The avoidance conditioning was seriously impaired in rats injected with aminochrome and dopachrome although only dopachrome-injected rats showed a similar hypomotility to 6-OHDA-injected rats. The behavioral effects were correlated to the extent of striatal tyrosine hydroxylase (TH)-positive fiber loss. Rats receiving unilateral intranigral aminochrome and dopachrome injections exhibited a 47.9+/-5.1% and a 39.7+/-4.4% reduction in nigrostriatal TH-positive fiber density. In conclusion, this study provided evidence that oxidizing DA and L-DOPA to cytotoxic quinones, aminochrome and dopachrome appears to be an important mediator of oxidative damage in vivo.

Animals↗

Inhibition of DT-diaphorase is a requirement for Mn(III) to produce a 6-OH-dopamine like rotational behaviour.

Intracerebral manganese administration together with the DT-diaphorase inhibitor dicoumarol [Mn(III) 40 nmol + -dicoumarol 2 nmol; in 4 micro l] into the left medial forebrain bundle (MFB) produced a behavioural pattern characterized by contralateral behaviour when the rats were stimulated with apomorphine (0.5 mg/kg s.c.), in a manner similar to that when administered to unilaterally 6-hydroxy-dopamine-lesioned animals. The same animals rotated towards the opposite side (ipsilaterally) when stimulated with d-amphetamine (2 mg/kg s.c.). These results support the idea that DT-diaphorase plays a protective role in the dopaminergic systems.

Journal Article↗

Bone mineral loss through increased bone turnover in HIV-infected children treated with highly active antiretroviral therapy.

OBJECTIVES: To evaluate the occurrence and define the aetiology of osteopenia in children receiving highly active antiretroviral therapy (HAART). METHODS: Bone mineral density (BMD) of total body and lumbar spine (L2-L4) was assessed by dual-energy X-ray absorptiometry in 40 children vertically infected with HIV: 35 taking HAART and five naive to any antiretroviral treatment (untreated). Six HAART-treated children showed clinical evidence of lipodystrophy. N-terminal propeptide of type-I procollagen (PINP), bone-specific alkaline phosphatase (BALP) and N-terminal telopeptide of type I collagen (NTx) were measured. Results were compared with those obtained in 314 healthy controls. Differences between HIV-positive and healthy children and within the HIV-positive group were assessed by multivariate analyses, controlling for confounding variables (age, sex, weight and height). RESULTS: HAART-treated children showed lower spine BMD values than untreated (P = 0.045) and healthy (P = 0.004) children and lower total body BMD values than untreated (P = 0.012) and healthy (P < 0.0001) children. Spine and total body BMD were similar between untreated and healthy children. Total body BMD was lower (P < 0.005) in HAART-treated children with lipodystrophy than in untreated patients, while children on HAART but without lipodystrophy had intermediate values. BALP, PINP and NTx were similar among untreated and healthy children. HAART-treated children had higher BALP levels than healthy (P = 0.0007) and untreated (P = 0.045) children. PINP values showed the same trend as BALP. HAART-treated children had higher NTx urine levels than healthy (P < 0.0001) and untreated (P = 0.041) children. CONCLUSIONS: HAART seems a new risk factor for life-long osteoporosis in children. An increased rate of bone turnover causes BMD decrease. Severity of osteopenia seems to be related to lipodystrophy.

Absorptiometry, Photon↗

Lipid raft microdomain compartmentalization of TC10 is required for insulin signaling and GLUT4 translocation.

Recent studies indicate that insulin stimulation of glucose transporter (GLUT)4 translocation requires at least two distinct insulin receptor-mediated signals: one leading to the activation of phosphatidylinositol 3 (PI-3) kinase and the other to the activation of the small GTP binding protein TC10. We now demonstrate that TC10 is processed through the secretory membrane trafficking system and localizes to caveolin-enriched lipid raft microdomains. Although insulin activated the wild-type TC10 protein and a TC10/H-Ras chimera that were targeted to lipid raft microdomains, it was unable to activate a TC10/K-Ras chimera that was directed to the nonlipid raft domains. Similarly, only the lipid raft-localized TC10/ H-Ras chimera inhibited GLUT4 translocation, whereas the TC10/K-Ras chimera showed no significant inhibitory activity. Furthermore, disruption of lipid raft microdomains by expression of a dominant-interfering caveolin 3 mutant (Cav3/DGV) inhibited the insulin stimulation of GLUT4 translocation and TC10 lipid raft localization and activation without affecting PI-3 kinase signaling. These data demonstrate that the insulin stimulation of GLUT4 translocation in adipocytes requires the spatial separation and distinct compartmentalization of the PI-3 kinase and TC10 signaling pathways.

Adipocytes↗

Rab4 affects both recycling and degradative endosomal trafficking.

The small GTPases Rab4, Rab5 and Rab7 are endosomal proteins which play important roles in the regulation of various stages of endosomal trafficking. Rab4 and Rab5 have both been localized to early endosomes and have been shown to control recycling and endosomal fusion, respectively. Rab7, a marker of the late endosomal compartment, is involved in the regulation of the late endocytic pathway. Here, we compare the role of Rab4, Rab5 and Rab7 in early and late endosomal trafficking in HeLa cells monitoring ligand uptake, recycling and degradation. Expression of the Rab4 dominant negative mutant (Rab4AS22N) leads to a significant reduction in both recycling and degradation while, as expected, Rab7 mutants exclusively affect epidermal growth factor (EGF) and low density lipoprotein degradation. As also expected, expression of the dominant negative Rab5 mutant perturbs internalization kinetics and affects both recycling and degradation. Expression of Rab4WT and dominant positive mutant (Rab4AQ67L) changes dramatically the morphology of the transferrin compartment leading to the formation of membrane tubules. These transferrin positive tubules display swellings (varicosities) some of which are positive for early endosomal antigen-1 and contain EGF. We propose that the Rab4GTPase is important for the function of the early sorting endosomal compartment, affecting trafficking along both recycling and degradative pathways.

Cell Compartmentation↗

Coronary Artery Disease in Postmenopausal Women.

Many important developments recently have been made in the treatment and prevention of coronary artery disease (CAD) in postmenopausal women. Substantial evidence supports focusing on comprehensive risk factor modification based on the "ABCs" of CAD management from the American College of Cardiology, the American Heart Association, and the American College of Physicians-American Society of Internal Medicine guidelines on chronic stable angina. This approach emphasizes cardiovascular risk factor interventions that include antiplatelet agents, angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, cholesterol-lowering medications, diabetes control, and counseling on diet and exercise. Despite the expanding available literature, many questions on CAD in postmenopausal women remain unanswered and await the publication of ongoing and future research. The unexpected findings from the HERS (Heart and Estrogen/progestin Replacement Study) failed to show a benefit of hormone replacement therapy (HRT) in reducing the risk of subsequent events in postmenopausal women with CAD, and instead reported an early increase in CAD events. Based on the data available so far, we advise against starting HRT in postmenopausal women with a recent coronary event for the sole purpose of CAD prevention. For women with acute coronary syndromes, prompt angiography and revascularization should be considered.

Journal Article↗

Effect of low dose tamoxifen on the insulin-like growth factor system in healthy women.

The use of tamoxifen as a preventive agent may be limited by the increased risk of endometrial cancer and venous thromboembolic events observed in postmenopausal women. We have recently shown a comparable activity of lower doses of tamoxifen on several surrogate biomarkers of cardiovascular disease and breast cancer, including Insulin-like Growth Factor-I (IGF-I). To provide further insight into the effect of tamoxifen at low doses on the IGF system, we have correlated the drug serum levels attained after 2 months of either placebo (n = 32), tamoxifen 20 mg/day (n = 26), 10 mg/day (n = 23) or 10 mg/every other day (n = 29) with the changes in IGF-I, Insulin-like Growth Factor-II (IGF-II), Insulin-like Growth Factor Binding Protein-1 (IGFBP-1), Insulin-like Growth Factor Binding Protein-3 (IGFBP-3), and IGF-I/IGFBP-3 ratio. Compared with placebo, tamoxifen induced a mean +/- standard error (SE) reduction of IGF-I of 16.9 +/- 7.8%, p < 0.05, a non-significant increase of 22.9 +/- 12.2% in IGF-II, an increase in IGFBP-1 of 49.3 +/- 22.7%, p < 0.05, and a non-significant change of IGFBP-3 (-4.0% +/- 9.2). No significant concentration-response relationship was observed between serum tamoxifen concentrations and the biomarker changes except for the ratio of IGF-I/IGFBP-3, which decreased by 1.53 +/- 0.68% for any increase by 10 ng/ml of serum tamoxifen concentration (p = 0.02). Although low tamoxifen concentrations induce a comparable modulation of the IGF family relative to the conventional dose, the lower decrements in the IGF-I/IGFBP-3 ratio observed at low drug concentrations might be associated with a reduced preventive activity. Further studies on the search of the minimal active dose of tamoxifen are warranted.

Anticarcinogenic Agents↗