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Biomedical subjects

A Hernandez

Publications and source records attributed to A Hernandez.

At least 73 records · Page 4Linked to original sources

Cyclooxygenase-2 and synthesis of PGE2 in human bronchial smooth-muscle cells.

The purpose of this study was to determine the mechanism of enhanced prostaglandin synthesis in cultured human bronchial smooth-muscle cells challenged with interleukin-1 beta (IL-1 beta). Cells were incubated with IL-1 beta (10 to 50 U/ml) for 0 to 24 h. Prostaglandin E2 (PGE2) production was evaluated through the conversion of exogenous (14C)-arachidonic acid and specific enzyme immunoassay of endogenous products. IL-1 beta enhanced PGE2 formation in a concentration- and time-dependent manner, reaching its peak at 6 to 8 h and fading at 18 to 24 h. Immunoblot analysis showed that the inducible cyclooxygenase enzyme (COX-2) was expressed only in IL-1 beta treated cells, whereas the constitutive isoform of cyclooxygenase (COX-1) remained unaltered. COX-2 expression and PGE2 formation were inhibited by dexamethasone (2 microM), cycloheximide (10 microM), and IL-1-receptor antagonist (IL-1 ra) (250 ng/ml), independently. PGE2 synthesis was significantly reduced by compound SC-58125, a specific COX-2 inhibitor. The close parallelism between the kinetics of COX-2 protein expression and PGE2 accumulation, as well as the constitutive nature of COX-1 isoform, indicate that IL-1 beta-driven PGE2 formation in human bronchial smooth-muscle cells is mediated by de novo expression of COX-2 enzyme.

Arachidonic Acid↗

Regulation of iodothyronine deiodinase activity as studied in thyroidectomized rats infused with thyroxine or triiodothyronine.

To provide new insights into the in vivo regulation of iodothyronine deiodinases in the different tissues of the rat, we have evaluated the effects on these enzymatic activities of T4 or T3 infusions into thyroidectomized rats. Thyroidectomized rats were infused with placebo, T4, or T3. Placebo-infused intact rats served as euthyroid controls. Plasma and samples of cerebral cortex, brown adipose tissue, pituitary, liver, and lung were obtained after 12-13 days of infusion. Plasma TSH, plasma and tissue T4 and T3, and iodothyronine deiodinase activities were determined. Type II 5'-deiodinase (DII) was increased in cortex, brown adipose tissue, and pituitary from animals infused with placebo. DII activity returned to normal only with T4 infusion, remaining elevated in the animals infused with T3 alone despite normal tissue T3 concentrations. Cortex type III 5-deiodinase was only increased when hyperthyroidism was induced by infusion of T3. Liver type I 5'-deiodinase (DI) paralleled the changes in plasma and tissue T3 regardless of whether T4 or T3 was infused. On the contrary, the increase in lung DI, proportional to the increases in plasma and tissue T3, was higher when T4 was infused. As a rule, the tissues with DII presented a tighter homeostasis in their T3 concentrations than the tissues with DI. In conclusion, the regulation of iodothyronine deiodinases depends on the hormone infused into the thyroidectomized animals and on the tissue in which the deiodinase is studied, demonstrating the existence of tissue-specific regulation of its thyroid hormone concentrations.

Adipose Tissue, Brown↗

High prevalence of mollusc shell hypersensitivity pneumonitis in nacre factory workers.

Following the discovery of hypersensitivity pneumonitis caused by the inhalation of mollusc shell dust in two workers from a nacre-button factory, the health status of 26 workers employed in sawing mollusc shells was investigated. The evaluation included the administration of two questionnaires and radiological, functional and immunological assessments of all workers at the outset and 1 year later, when hygienic and therapeutic measures had been taken. Six workers, in whom specific inhalation challenge test was positive, were diagnosed with mollusc shell hypersensitivity pneumonitis, thus yielding a prevalence of 23%. Evidence of diffuse lung disease and systemic symptoms was found in these patients. Nonspecific bronchial hyperreactivity was also found more frequently in patients with mollusc shell hypersensitivity pneumonitis. Specific immunoglobulin G (IgG) level and specific skin testing failed to differentiate patients with mollusc shell hypersensitivity pneumonitis from other exposed workers; whereas, nonspecific skin testing, which was impaired in the patients, did differentiate. Bronchoalveolar lavage and transbronchial biopsy performed in patients with mollusc shell hypersensitivity pneumonitis were consistent with the disease. Removal from an environment containing mollusc shell dust was followed by regression of clinical, radiological and functional changes. The clinical picture of the 20 workers who did not present mollusc shell hypersensitivity pneumonitis remained unchanged, but functional decline was observed despite improvement in the environmental conditions of the factory. This report describes the first series of patients with mollusc shell hypersensitivity pneumonitis studied, and underlines the importance of careful follow-up of workers occupationally-exposed to mollusc shell dust.

Adult↗

Transrectal prostate ultrasonography: variability of interpretation.

PURPOSE: The current study was designed to compare the interpretation of the individual performing transrectal ultrasound examination (operator) with experienced individuals who interpreted the examination with and without the availability of clinical data. Inter-observer and intra-observer variability was compared to determine the reproducibility and reliability of the study. MATERIALS AND METHODS: All patients undergoing radical prostatectomy for treatment of localized carcinoma of the prostate underwent a transrectal ultrasound examination before the procedure. The sonogram was interpreted by the operator and reviewers. The radical prostatectomy specimen was examined pathologically and the staging as determined by ultrasound was compared with the pathological findings. RESULTS: Ultrasound operator accuracy for extracapsular extension and seminal vesicle invasion was 0.70 and 0.74, respectively, compared with the accuracy of the reviewers, which ranged from 0.59 to 0.75 and 0.44 to 0.74 for extracapsular extension and seminal vesicle invasion, respectively. In general, blinded reviews were less accurate than unblinded reviews but this was only statistically significant for 2 reviewers. CONCLUSIONS: Although for most reviewers the addition of clinical data did not improve the accuracy of the interpretation, an advantage was noted for the operator, that is, the individual performing the examination. In general, the technical quality of the examination was related to the accuracy of the readings.

Humans↗

Susceptibility of Lutzomyia longipalpis (Diptera: Psychodidae) to selected insecticides in an endemic focus of visceral leishmaniasis in Venezuela.

A field population of Lutzomyia longipalpis from La Rinconada, Lara State, an endemic focus of visceral leishmaniasis in Venezuela, was tested for susceptibility to organochlorine (DDT 2%), carbamate (propoxur 0.01%), organophosphate (malathion 2%, fenitrothion 1%, and pirimiphos methyl 1%), and pyrethroid (deltamethrin 0.06%, lambdacyhalothrin 0.06%, and permethrin 0.2%) insecticides. Susceptibility to the insecticides tested was evaluated in the field population of L. longipalpis and compared with a laboratory reference strain. The (LT95) to propoxur and malathion insecticides for the field population was lower than the LT95 for the laboratory reference strain, demonstrating high susceptibility to these compounds. A low level of resistance at LT50 (< 3-fold) was found for fenitrothion, pirimiphos methyl, and permethrin insecticides, but no resistance was detected at LT95. No significant resistance at the LT50 and LT95 was detected for the pyrethroids deltamethrin and lambdacyhalothrin. The susceptibility levels of L. longipalpis to the insecticides tested are discussed in view of a future control program against endophilic vectors of leishmaniases based on the use of pesticides.

Animals↗

Direct effect of phosphorus on PTH secretion from whole rat parathyroid glands in vitro.

Phosphorus retention is an important factor in the development of hyperparathyroidism secondary to renal failure. In vivo manipulation of phosphorus is associated with changes in serum calcium and calcitriol levels which in turn can modify parathyroid hormone synthesis and secretion. The present in vitro study evaluates whether high extracellular phosphorus has a direct effect on parathyroid hormone secretion. Fresh rat parathyroid glands were incubated in a media with phosphorus concentrations of 1, 2, 3, and 4 mM and subsequently exposed to calcium levels ranging from 0.4 to 1.35 mM. In 1.25 mM calcium, the parathyroid hormone secretion rate was similar in 1 and 2 mM phosphorus; however, a phosphorus concentration of 3 and 4 mM produced a 3- and 4-fold increase in the parathyroid hormone secretion, respectively, as compared with 1 mM phosphorus. While in 1 or 2 mM phosphorus an increase in calcium from 0.6 to 1.35 mM reduced parathyroid hormone secretion to 37%, in 4 mM phosphorus the same increase in calcium only inhibited parathyroid hormone secretion to 75%. Furthermore, the addition of arachidonic acid 20 microM, a substrate for inhibitory intracellular signal pathway, to the 4 mM phosphorus-1.35 mM calcium incubation media reduced the parathyroid hormone secretion to 34.5% (p < 0.05). In conclusion, our results indicate that in vitro, high phosphorus directly increases parathyroid hormone secretion.

Analysis of Variance↗

Spatial compounding in ultrasonic imaging using an articulated scan arm.

A spatial compounding system has been designed to improve the quality of B-mode echographic images. It consists of constructing an improved image from the combination of several different images of the same cross-sectional plane. The "final" image is constructed by the registration and the superposition of the "original" images. For this, the relative position in the space of the original images has to be known. The use of a localization articulated arm, on which the ultrasonic probe is fixed, makes this possible. The main advantages of the technique are, on one hand, the elimination of the acoustic shadows following a strong reflector structure and, on the other hand, the reduction of the speckle generated in echographic images. The method of reconstruction has been validated on agar gel phantoms and provides good accuracy. In vivo experiments on human beings have also been performed. Acoustic shadows caused by bones in cross-sectional images of the thigh and the arm are eliminated. All the contours of the femur and humerus can be observed in the final images. The reduction of speckle is shown in kidney images and the signal-to-noise ratio improvement is quantified as a function of the number of images involved in the reconstruction.

Agar↗

Increased matrix metalloproteinase activity and reduced tissue inhibitor of metalloproteinases-1 levels in amniotic fluids from pregnancies complicated by premature rupture of membranes.

OBJECTIVES: It has been suggested that increased matrix metalloproteinases activity promotes the weakening of the amniochorion during normal and premature rupture of membranes. This study was designed to determine whether levels of matrix metalloproteinases and the tissue inhibitor of metalloproteinases-1 in amniotic fluid change in a pattern consistent with this hypothesis. STUDY DESIGN: Gelatinolytic activity, measured by a soluble substrate assay and zymography, and the concentrations of tissue inhibitor of metalloproteinases-1 were estimated in amniotic fluid obtained from (1) normal early gestations, (2) normal term pregnancies with labor, (3) normal term pregnancies without labor, and (4) pregnancies complicated by premature rupture of membranes. The 92 kd type IV collagenase (matrix metalloproteinase-9) was also detected in amniotic fluid by Western blotting. RESULTS: Matrix metalloproteinase activities were higher in amniotic fluid from normal term pregnancies with labor and pregnancies complicated by premature rupture of membranes than from early pregnancies and term gestations without labor. The amniotic fluid from term pregnancies with labor or pregnancies with premature rupture of membranes contained several gelatinases, as revealed by zymography. The major amniotic fluid gelatinolytic activity in premature rupture of membranes and term pregnancies with labor corresponded to matrix metalloproteinase-9. Tissue inhibitor of metalloproteinases-1 concentrations were highest in early-pregnancy amniotic fluid, followed by term gestation with labor, term gestation without labor, and premature rupture of membranes. CONCLUSIONS: Normal labor and premature rupture of membranes are associated with increased levels of matrix metalloproteinases, particularly matrix metalloproteinase-9 in amniotic fluid. Premature rupture of membranes is associated with reduced levels of tissue inhibitor of metalloproteinases-1. The imbalance between matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 in amniotic fluid may reflect a disorder that promotes premature rupture of membranes.

Amniotic Fluid↗

Relative effects of PTH and dietary phosphorus on calcitriol production in normal and azotemic rats.

In moderate renal failure, the serum calcitriol level is influenced by the stimulatory effect of high PTH and the inhibitory action of phosphorus retention. Our goal was to evaluate the relative effect that high PTH levels and increased dietary phosphorus had on calcitriol production in normal rats (N) and rats with moderate renal failure (Nx). Normal and Nx (3/4 nephrectomy) rats were divided into two groups: (1) rats with intact parathyroid glands (IPTG) and (2) parathyroidectomized rats in which PTH was replaced (PTHR) by the continuous infusion of rat 1-34 PTH, 0.022 microgram/hr/100 g body wt, using a miniosmotic Alzet pump. To test the effect of dietary phosphorus, rats received either a moderate (MPD, 0.6% P) or a high phosphorus (HPD, 1.2%) diet for 14 days. The experimental design included pair-fed N and Nx rats with either IPTG or PTHR. Serum calcitriol and PTH levels in N rats fed a MPD were 69 +/- 3 and 40 +/- 5 pg/ml, respectively. In Nx rats on a MPD, serum calcitriol levels decreased only if hyperparathyroidism was not allowed to occur (76 +/- 4 vs. 62 +/- 4 pg/ml in Nx-IPTG-MPD and Nx-PTHR-MPD groups respectively, P < 0.05). Even in N rats on a HPD, high PTH levels (67 +/- 8 pg/ml in the N-IPTG-HPD group) were required to maintain normal serum calcitriol levels (69 +/- 4 vs. 56 +/- 6 pg/ml in Nx-IPTG-HPD and Nx-PTHR-HPD groups, respectively; P < 0.05). In Nx rats on a HPD, the development of secondary hyperparathyroidism (286 +/- 19 pg/ml in the Nx-IPTG-HPD group) prevented a decrease in serum calcitriol levels (68 +/- 7 pg/ml). In contrast, serum calcitriol levels were low in the Nx-PTHR-HPD group (52 +/- 4 pg/ml, P < 0.05), which were deprived of the adaptative increase in endogenous PTH production. In conclusion, our results in rats indicate that in moderate renal failure, an elevated PTH level maintains calcitriol production and overcomes the inhibitory action of phosphorus retention.

Animals↗

Effect of phosphate on the parathyroid gland: direct and indirect?

Hyperparathyroidism is a common finding in patients with renal failure. Phosphorus retention is known to be an important factor in the development of secondary hyperparathyroidism. Exciting new work has demonstrated that a high extracellular phosphorus concentration directly stimulates parathyroid hormone secretion and synthesis. Dietary phosphorus also modulates parathyroid function indirectly by decreasing calcitriol production, and it interferes with the calcaemic response to parathyroid hormone. The information available suggests that the control exerted by phosphorus is critical, via indirect and direct actions, in preventing the development of secondary hyperparathyroidism.

Animals↗

Naturally azole-resistant Leishmania braziliensis promastigotes are rendered susceptible in the presence of terbinafine: comparative study with azole-susceptible Leishmania mexicana promastigotes.

Leishmania braziliensis (isolate 2903) was naturally resistant to ketoconazole or the bis-triazole D0870, inhibitors of sterol C-14 demethylase, which produced only moderate effects on the proliferation of promastigotes at 10 microM. In contrast, Leishmania mexicana (isolate NR) was extremely susceptible to the azoles, as complete growth arrest and cell lysis were induced by incubation of the parasites with 0.05 microM concentrations of the drugs for 72 h. The opposite response was observed with terbinafine, an inhibitor of squalene epoxidase: L. braziliensis 2903 was three times more susceptible to the drug than L. mexicana NR (MICs of 5 and 15 microM, respectively). However, when the L. braziliensis stock was grown in the presence of 1 microM terbinafine, which by itself produced only marginal (< 10%) effects on growth, it became highly susceptible to the azoles, with an MIC of 0.03 microM. Analysis of cellular free sterols by high-resolution capillary gas chromatography coupled to mass spectrometry showed that 14-methyl sterols can support normal growth of L. braziliensis 2903 but not of L. mexicana NR. On the other hand, the higher susceptibility of the L. braziliensis isolate to terbinafine was correlated with a massive accumulation of squalene in the presence of the allylamine while no significant effects on L. mexicana sterol composition were observed at drug concentrations up to 1 microM. Thus, the > 300-fold increase in the susceptibility of L. braziliensis promastigotes to azoles in the presence of terbinafine was attributed to the combined effect of squalene and the methylated sterol precursors on the physical properties of the cell's membranes, leading to the loss of cell viability. Combination therapy with azoles and terbinafine in the treatment of human L. braziliensis infections deserves further study.

Animals↗

Cross-tolerance to acute administration of mu and kappa opioid agonists at the spinal cord level in the rat.

Development of tolerance and cross-tolerance after acute administration of the mu agonist morphine and the kappa agonist U-50,488H was assessed in rats, through recording of a C-fiber-evoked spinal nociceptive reflex. Rats rendered tolerant to morphine (a single dose of 1 mg/kg i.p.) showed, after a 5-hour period, tolerance to morphine and cross-tolerance to the kappa-opioid receptor agonist U-50,488H, as revealed by depressed C-reflex responsiveness. In contrast, pretreatment with U-50,488H (a single dose of 1 mg/kg i.p.) rendered tolerant the rats to U-50,488H, but the animals did not develop cross-tolerance to morphine. Results indicate that acute administration of mu and kappa ligands leads to development of unidirectional cross-tolerance in rat spinal cord. This points to limitations in using alternated mu and kappa opioid agonists to bypass the problem of development of opioid tolerance in chronic pain complaints.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Gender priming in Italian.

The goals of the present study were (1) to determine whether grammatical gender on a noun modifier can prime recognition of the following noun, (2) to determine whether the priming effect involves facilitation, inhibition, or both, and (3) to compare performance across three different tasks that vary in the degree to which explicit attention to gender is required, including word repetition, gender monitoring, and grammaticality judgment. Results showed a clear effect of gender priming, involving both facilitation and inhibition. Priming was observed whether or not the subjects' attention was directed to gender per se. Results suggest that gender priming involves a combination of controlled postlexical processing and automatic prelexical processing. Implications for different models of lexical access are discussed, with special reference to modular versus interactive-activation theories.

Adult↗

Prevalence of malnutrition in Mexican CAPD diabetic and nondiabetic patients.

Malnutrition is often present on continuous ambulatory peritoneal dialysis (CAPD), and contributes to morbidity and mortality. Diabetics (DM) have an increased risk for developing malnutrition. Our purpose was to assess the nutritional status (NS) of our CAPD population, to define NS differences between DM and nondiabetics (NoDM), and to identify NS-related factors. Patients were subjected to a nutritional assessment, which included a 24-hour dietary recall and a nutritional scoring system including anthropometric, biochemical, and subjective evaluation, and that classifies patients as: normal, and mildly, moderately, and severely malnourished. We studied 90 patients: 35 DM and 55 NoDM. In our whole population we observed a high frequency of malnutrition: NS was normal in 18%, and 20% had mild, 24% had moderate, and 38% had severe malnutrition. Ninety-one percent of DM and 76% of NoDM showed some degree of malnutrition. DM patients had significantly higher levels of malnutrition (p = 0.02), were significantly older, had more body fat, and spent less time on dialysis. There were 37 males and 53 females. Sex distribution was similar between DM and NoDM. Seventy-six percent of males and 86% of females had malnutrition. Moderate and severe malnourishment were more frequent in females. DM and female sex were the strongest predictors for moderate and severe malnutrition.

Adult↗

Qualitative assessment of mixed chimerism after allogeneic bone marrow transplantation with regard to leukemic relapse.

Serial peripheral blood specimen from eight adult patients after sex-mismatched bone marrow transplantation (BMT) for Chronic Myeloid Leukemia (CML) (N = 3). Ewing sarcoma (N = 1), Acute Myeloid Leukemia (AML) in second remission (N = 1), Acute Lymphoid Leukemia (ALL) (N = 1), of multiple myeloma (N = 2) were analyzed by the simultaneous immunophenotypic (moAbs/ APAAP-staining) and genotypic analysis (for X and Y chromosomes) of interphase cells to characterize mixed chimerism, residual host cells, and leukemic relapse. Although a stable donor chimerism for T cells, myelomonocytic cells, and granulocytes was developed in seven of the eight patients at Days +21 to +28 post BMT, 0.5 to 1% host cells of different lineages remained continuously in five of the eight patients post BMT (> day 100). In two patients, one with common ALL and the other with multiple myeloma and long-term stable mixed chimerism, a tumor cell relapse was detected first in a sample at Day +176 and confirmed at Day +294. These malignant cells were genotypically of host origin and presented phenotypes identical to those at diagnosis. In the three patients with CML, residual host cells were identified as CD13 (Patient 3) of CD13/CD34 (Patient 4) positive and in one case as CD4/CD8 positive (Patient 7). Since no exclusive antigenic marker is available for this discrimination in these CML patients, normal host hematopoiesis can interfere with the identification of residual disease. Therefore, the identification of the bcr-abl transcripts by a two-step reverse transcriptase-polymerase chain reaction (RT-PCR) was included in this analysis. Patient 3 was bcr-abl positive at [Days +21, +28, +35, and +311, but negative at Days +121 and +400; Patient 4 was bcr-abl positive at only Day +166 post BMT. These results are interpreted as signaling a continuing risk of relapse. In Patient 7, the bcr-abl RT-PCR was negative at Days +142, +166, and +237. Thus, the combination of the simultaneous immunophenotypic and genotypic analysis and the bcr-abl detection by RT-PCR clearly improves the discrimination between malignant cells and normal residual host cells.

Acute Disease↗

Mevalonate pathway and isoprenoids regulate human bronchial myocyte proliferation.

The role of mevalonate and geranylgeraniol in the control of cellular proliferation of cultured human bronchial myocytes was examined by investigating the effect of simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme in mevalonate synthesis. Simvastatin inhibited the rate of growth of human bronchial smooth muscle cells in a concentration-dependent manner, with an IC50 value of 0.97 +/- 0.1 microM. Mevalonate (100 microM), as well as geranylgeraniol (5 microM), at their highest non-toxic concentrations, restored cell proliferation to control levels.

Bronchi↗

Immune depression induced by protein calorie malnutrition can be suppressed by lesioning central noradrenaline systems.

Depressed immune function is well documented in protein calorie malnutrition (PCM). Also, central noradrenergic hyperactivity has recently been reported in malnourished animals. Increase in central noradrenaline activity could be responsible for cell-mediated immune depression. The present study is designed to address this hypothesis by testing whether neurotoxic lesion of central noradrenergic systems by 6-hydroxydopamine (6-OHDA) could improve lymphoproliferative response to mitogens and interleukin (IL)-1 production in PCM rats. A significant enhancement of lymphoproliferative response to concanavalin A (ConA) and in IL-1 production was observed in spleen mononuclear cells of PCM rats injected intracerebroventricularly with 120 micrograms of 6-OHDA, as compared with solvent injected and untreated PCM animals. A significant decrease in brain noradrenaline levels was produced in the drug-injected animals. These results suggest that central noradrenergic hyperactivity is one of the mechanisms involved in the immunodepression produced by malnutrition.

Animals↗