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Biomedical subjects

M Saavedra

Publications and source records attributed to M Saavedra.

At least 19 recordsLinked to original sources
PubMed2006

Mice deficient in galectin-1 exhibit attenuated physiological responses to chronic hypoxia-induced pulmonary hypertension.

Pulmonary hypertension (PH) is characterized by sustained vasoconstriction, with subsequent extracellular matrix (ECM) production and smooth muscle cell (SMC) proliferation. Changes in the ECM can modulate vasoreactivity and SMC contraction. Galectin-1 (Gal-1) is a hypoxia-inducible beta-galactoside-binding lectin produced by vascular, interstitial, epithelial, and immune cells. Gal-1 regulates SMC differentiation, proliferation, and apoptosis via interactions with the ECM, as well as immune system function, and, therefore, likely plays a role in the pathogenesis of PH. We investigated the effects of Gal-1 during hypoxic PH by quantifying 1) Gal-1 expression in response to hypoxia in vitro and in vivo and 2) the effect of Gal-1 gene deletion on the magnitude of the PH response to chronic hypoxia in vivo. By constructing and screening a subtractive library, we found that acute hypoxia increases expression of Gal-1 mRNA in isolated pulmonary mesenchymal cells. In wild-type (WT) mice, Gal-1 immunoreactivity increased after 6 wk of hypoxia. Increased expression of Gal-1 protein was confirmed by quantitative Western analysis. Gal-1 knockout (Gal-1(-/-)) mice showed a decreased PH response, as measured by right ventricular pressure and the ratio of right ventricular to left ventricular + septum wet weight compared with their WT counterparts. However, the number and degree of muscularized vessels increased similarly in WT and Gal-1(-/-) mice. In response to chronic hypoxia, the decrease in factor 8-positive microvessel density was similar in both groups. Vasoreactivity of WT and Gal-1(-/-) mice was tested in vivo and with use of isolated perfused lungs exposed to acute hypoxia. Acute hypoxia caused a significant increase in RV pressure in wild-type and Gal-1(-/-) mice; however, the response of the Gal-1(-/-) mice was greater. These results suggest that Gal-1 influences the contractile response to hypoxia and subsequent remodeling during hypoxia-induced PH, which influences disease progression.

Animals↗
PubMed2006

Enzyme activities and chemical changes in wet olive cake after treatment with Pleurotus ostreatus or Eisenia fetida.

A laboratory experiment was conducted to evaluate the enzyme activities and chemical changes recorded in a recalcitrant phenolic-rich waste after treatment with Pleurotus ostreatus or Eisenia fetida. The waste used was wet olive cake (alperujo in Spanish), a waste produced in huge amounts by the olive oil industry. Both P. ostreatus and E. fetida were very effective in removing phenolic compounds, the initial concentration in the wet olive cake being reduced in both cases by around 90%. Laccase and manganese peroxidase activities were measured in the growth medium of P. ostreatus, and catechol 2,3 dioxygenase activity was only detected in the waste treated with Eisenia; these could be the main factors responsible for the oxidation of phenolic compounds. Increases of dehydrogenase and beta-glucosidase activities were detected in the degraded wet olive cake by fungi or earthworms. In comparison with the natural wet olive cake, the degraded products had lower total organic carbon and humic acid contents but were rich in nitrogen and other nutrients, having lower C:N ratios. In addition, the toxicity of the wet olive cake against the seeds of Lepidium sativum significantly decreased after degradation. The low toxicity as well as moderate stability and maturity recorded in the wet olive cake treated with P. ostreatus or E. fetida imply that these products could be used as soil amendments.

Animals↗
PubMed2006

Timely diagnosis of MDR-TB under program conditions: is rapid drug susceptibility testing sufficient?

Timely diagnosis and effective, safe treatment are essential to reduce transmission and improve outcomes for patients with tuberculosis. Aside from laboratory methods, many programmatic factors influence the overall turnaround time (TAT) in diagnosing multidrug-resistant tuberculosis (MDR-TB). We measured each step in the overall TAT required for MDR-TB in two of five health districts of Lima, Peru. The total TAT, from initial sputum specimen to diagnosis and appropriate treatment, was 5 months, almost twice as long as the bacteriological procedures per se. Expensive investments in laboratory technology may yield low returns unless the programmatic aspects of the diagnostic process are streamlined at the same time.

Antibiotics, Antitubercular↗
PubMed2000

In vivo virulence of Candida albicans isolates causing mucosal infections in people infected with the human immunodeficiency virus.

Mucosal candidiasis is common in human immunodeficiency virus (HIV) infection. Susceptibility to such infections may be attributed to reduced host defense mechanisms and/or virulence of the organism. In the present study, we compared the virulence of mucosal Candida albicans isolates from HIV-infected people, with and without fluconazole-refractory infection, in established murine models of systemic and vaginal candidiasis. Compared with the mortality rate ( approximately 70%) after intravenous challenge with 2 virulent reference isolates, challenge with most clinical isolates (66%-77%) resulted in prolonged survival. In contrast, fungal burden induced by intravaginal challenge of nearly all (97%) isolates was similar to that of the virulent controls. There were no differences in in vitro growth rates for any of the isolates, and there was no association between reduced mortality and clinical failure to fluconazole, in vitro antifungal susceptibility, site of infection, or other host factors. These results suggest that virulence of C. albicans is tissue specific and is not a factor in the development of fluconazole-refractory infections in advanced HIV disease.

AIDS-Related Opportunistic Infections↗
PubMed2000

Lateral septal neuronal firing rate increases during proestrus-estrus in the rat.

Neuronal activity of the lateral septal nucleus (LSN) is related to motivational and hedonic behavior. Even though some changes in mood and anxiety during proestrus and pregnancy have been reported, the possible changes in the neuronal activity of the LSN through the phases of the estrous cycle are unknown. In the present study we explored the neuronal activity from the LSN using glass micropipettes (NaCl 1 M, and Evans blue 2.5%; 3-8 Mohms in 30 urethane (1 g/kg) anesthetized Wistar rats. Analysis of data included a total of 88 single-unit extracellular recordings taken from the LSN during proestrus (n = 22), estrus (n = 23), diestrus (n = 22), and metestrus (n = 21). The highest values of firing rate were found in proestrus, and the lowest in metestrus, F(3,84) = 3.78, p < 0.01. During estrous cycles, in the phase characterized by high plasma levels of estradiol and progesterone, i.e., proestrus-estrus, the neurons from the dorsal aspect of the LSN fired at significantly (p < 0.05) higher frequencies, shorter first-order intervals and a lower coefficient of variation than those in the phase characterized by lower levels of estradiol and progesterone (metestrus-diestrus). In another group of rats (n = 12), immobility in the forced-swim test was assessed. Consistently, a longer latency (p < 0.05) for the first period of immobility and a nonsignificant trend to a lowered total time in immobility were found in proestrus and estrus. It is concluded that the higher firing rate in neurons from the dorsal aspect of the LSN during proestrus-estrus, may be associated with an increased motivation to escape from a stressful situation.

Affect↗
PubMed2000

Local Th1/Th2 cytokine production during experimental vaginal candidiasis: potential importance of transforming growth factor-beta.

Host defense mechanisms against vaginal Candida albicans infections are poorly understood. Despite the protective role of T helper (Th)1-type cell-mediated immunity (CMI) against mucosal C. albicans infections, studies using an estrogen-dependent murine model of vaginal candidiasis have shown a lack of effect of systemic Th1-type CMI against a vaginal C. albicans infection, and a lack of changes in local T cells during infection. In the present study, the local Thl- (interleukin [IL]-2, interferon [IFN]-gamma and IL-12) and Th2- (IL-4, IL-10 and transforming growth factor [TGF]-beta1) type cytokines were evaluated in vaginal tissue during an experimental C. albicans infection. Results showed constitutive expression of TGF-beta1 in vaginal tissue of naive mice that was two-fold higher than the levels of the other cytokines examined. These high levels of TGF-beta1 were further increased as a result of pseudoestrus and/or infection, and were corroborated at the messenger RNA level. Furthermore, the levels of TGF-beta in naive or infected mice were significantly higher in the vagina compared to other areas of the genital tract. Finally, TGF-beta1 predominated as well in the draining, but not non-draining, lymph nodes during infection. These results suggest that TGF-beta1, a potent immunoregulatory cytokine, may be important in the lack of demonstrable CMI at the vaginal mucosa against C. albicans.

Animals↗
PubMed1999

Simultaneous determination of chlordiazepoxide and clidinium bromide in pharmaceutical formulations by derivative spectrophotometry.

A direct and simple first derivative spectrophotometric method has been developed for the simultaneous determination of clidinium bromide and chlordiazepoxide in pharmaceutical formulations. Acetonitrile was used as solvent for extracting the drugs from the formulations and subsequently the samples were evaluated directly by derivative spectrophotometry. Simultaneous determination of the drugs can be carried out using the zero-crossing method for clidinium bromide at 220.8 nm and the graphical method for chlordiazepoxide at 283.6 nm. The calibration graphs were linear in the ranges from 0.983 to 21.62 mg/l of clidinium bromide and from 0. 740 to 12.0 mg/l of chlordiazepoxide. The ingredients commonly found in commercial pharmaceutical formulations do not interfere. The proposed method was applied to the determination of these drugs in tablets.

Acetonitriles↗
PubMed1999

Local production of chemokines during experimental vaginal candidiasis.

Recurrent vulvovaginal candidiasis, caused by Candida albicans, is a significant problem in women of childbearing age. Although cell-mediated immunity (CMI) due to T cells and cytokines is the predominant host defense mechanism against C. albicans at mucosal tissue sites, host defense mechanisms against C. albicans at the vaginal mucosa are poorly understood. Based on an estrogen-dependent murine model of vaginal candidiasis, our data suggest that systemic CMI is ineffective against C. albicans vaginal infections. Thus, we have postulated that local immune mechanisms are critical for protection against infection. In the present study, the kinetic production of chemokines normally associated with the chemotaxis of T cells, macrophages (RANTES, MIP-1alpha, MCP-1), and polymorphonuclear neutrophils (MIP-2) was examined following intravaginal inoculation of C. albicans in estrogen-treated or untreated mice. Results showed significant increases in MCP-1 protein and mRNA in vaginal tissue of infected mice as early as 2 and 4 days postinoculation, respectively, that continued through a 21-day observation period, irrespective of estrogen status. No significant changes were observed with RANTES, MIP-1alpha, or MIP-2, although relatively high constitutive levels of RANTES mRNA and MIP-2 protein were observed. Furthermore, intravaginal immunoneutralization of MCP-1 with anti-MCP-1 antibodies resulted in a significant increase in vaginal fungal burden early during infection, suggesting that MCP-1 plays some role in reducing the fungal burden during vaginal infection. However, the lack of changes in leukocyte profiles in vaginal lavage fluids collected from infected versus uninfected mice suggests that MCP-1 functions to control vaginal C. albicans titers in a manner independent of cellular chemotactic activity.

Animals↗
PubMed1998

Desipramine restricts estral cycle oscillations in swimming.

1. Desipramine (DMI) is a tricyclic antidepressant which reduces the immobility in rats forced to swim; however, it is unknown whether estral cycle phases impinge on DMI actions on immobility in daily swimming tests during several weeks. 2. In female wistar rats, vaginal smears taken before testing defined four estral phases. Afterwards, the authors assessed the latency for the first period of immobility in five-min forced swim tests practiced on 21-day DMI (DMI group), 21-day washout saline given after a 21-day DMI treatment (washout-saline group), or non-treated rats (control group). 3. We observed a longer latency for the first period of immobility in proestrus-estrus from the control and washout-saline groups. The 21-day treatment with DMI (2.1 mg/kg i.p., once a day) significantly (p < 0.001) increased the latency by about 160% from control regardless of the estral cycle phase. 4. It is concluded that proestrus-estrus relates to increased struggling behavior. DMI enhances struggling behavior independently of hormonal state.

Animals↗
PubMed1996

Raphe-septal neurons changes in sensitivity to desipramine following an early septal lesion in the rat.

1. The electrophysiological responsivity to desipramine (DMI) applied by systemic or local route was tested in Wistar female rats submitted to a wide lesion in the lateral septal area on the 8th day after birth. 2. One year after a septal lesion, the dorsal raphe nucleus (DRN) stimulation produced an initial brief response in lateral septal and CA1/CA3 neurons. In the control and sham-lesion groups, most recordings showed only this initial brief response (non-late responding neurons); however, in the lesion group most of the recorded neurons showed an afterdischarge. 3. DMI (2.14 mg/kg, 21 days, i.p.) increased the firing rate in septal and CA1/CA3 non-late responding neurons. In the equivalent septal neurons from lesion group, DMI produced the inverse effect, i.e., a decreased firing rate. 4. In septal non-late responding neurons, DMI (2 mM; 10-15 nAmps, 0.5 sec) applied by microiontophoresis increased the firing rate only after long-term systemic DMI impregnation. The response to locally applied DMI did not occur in the lesion group even after long-term DMI treatment. 5. In conclusion, an early lateral septal lesion canceled the response of intermediate-dorsal septal neurons to DMI applied by systemic and local routes.

Animals↗
PubMed1996

Curve walking in crayfish

Curve walking of crayfish Astacus leptodactylus was investigated by exploiting their optomotor response. The animal walked while spatially fixed on a motor-driven treadmill and turning behaviour was induced by an optical stimulus, a pattern consisting of vertical stripes moving in a horizontal direction. In this open-loop situation, the crayfish maintains the same step frequency for the legs on both sides of the body for low and intermediate turning speeds, but increases the step amplitude of the outer legs 2, 3 and 4 by shifting the posterior extreme position (PEP) of these legs in a posterior direction and reduces the step amplitude of inner leg 5 by shifting the PEP of this leg in an anterior direction. Furthermore, the main movement direction of the legs can change relative to the body. This was observed for outer leg 5 and also, at higher turning speeds, for outer leg 2. As coordinating influences between contra- and ipsilateral legs were found directly to influence only the anterior extreme position of the legs, these results indicate that the mechanisms controlling curve walking may be different from those controlling normal leg coordination.

Journal Article↗
PubMed1995

The combination of several antidepressants is not synergistic on the firing of lateral septal neurons in the rat.

1. Three kinds of antidepressants (clomipramine, sleep deprivation, and electroconvulsive shock) increase the firing rate in the lateral septal neurons of the rat. 2. The acute combination of these treatments, however, did not produce added effects on firing rate of lateral septal neurons in the rat. 3. 24 hours of sleep deprivation blocked the actions of a single electroconvulsive shock. 4. It is concluded that the firstly applied treatment modifies the receptors sensitivity from the very beginning, thus blocking the action of a second treatment.

Animals↗
PubMed1995

An early lesion of the lateral septal nuclei produces changes in the forced swim test depending on gender.

1. Several pharmacological maneuvers in very young rats produce later changes resembling human depression. 2. Rats were submitted to a wide lesion in lateral septal region at 8th day after birth and forced to swim at maturity. 3. Male lesioned group showed the highest amount of immobility; whereas, female sham lesion group showed a greater response to treatments. 4. A gender-dependent sensitivity to early lateral septal nucleus lesions and to antidepressants are concluded.

Animals↗
PubMed1993

[Anxiety and depression levels in rape offenders].

Whether the active subject of rape possesses a particular personality trait is a much debated matter. It is an accepted fact that a small amount of rapists fall into the sadistic diagnostic category. Other psychopatologic traits likely to identify a rapist are, however, unknown. The present study was carried over at a jail near the city of Xalapa (Veracruz) Mexico. Hamilton, IDARE, and Zung scales, in their modified Spanish version were applied to a sample of imprisoned adult rapists. Compared to their control group (men serving sentences for other felonies), rapists scored higher in anxiety, and depression scales. In the light of these results, it is suggested that some rapists are likely to be anxious-depressive subjects that, after having "acquired" a sociopathic repertoire, offend other people in conditions of indefensiveness, contrary to depressive subjects who aggress themselves.

Adult↗
PubMed1992

Deferoxamine increases the susceptibility of beta-thalassemic, iron-overloaded mice to infection with Listeria monocytogenes.

The effect of the iron chelator deferoxamine (DFO) on resistance to infection with Listeria monocytogenes in mice with a condition analogous to human beta-thalassemia was studied. Intraperitoneal injection of 10 mg DFO resulted in significantly increased mortality when given one, three and six days before infection with L. monocytogenes (for all three time points, p less than 0.02). There were no significant differences in hematocrit, plasma iron, or splenic iron content between the two groups of mice during these time periods. In addition, splenic counts of L. monocytogenes were not significantly higher in DFO-treated compared to saline-treated mice three days after infection. Moreover, background C57Bl/6J mice were not more susceptible to Listeria infection after receiving DFO than were saline-treated controls. In conclusion, acute administration of DFO increases the susceptibility of beta-thalassemic mice to L. monocytogenes. The effect is not seen in background mice and suggests that DFO increases susceptibility to Listeria infection only in animals with iron overload.

Animals↗