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Biomedical subjects

R Hernández

Publications and source records attributed to R Hernández.

At least 19 recordsLinked to original sources

Electrosurgical endoscopic cordectomy with microdissection electrodes: a comparative study with CO2 laser.

Microdissection electrodes (MEs) have previously been used to perform endoscopic cordectomies. We designed a prospective study in order to compare the ME with the CO2 laser technique. Over two years, 20 patients with T1 glottic carcinoma were operated on with CO2 laser and 20 with MEs. The device was chosen alternatively for each new patient. Two patients in both treatment groups had slight glottic incompetence. Three patients in each group showed web formation. The only granuloma was observed in a CO2 laser patient. Seven of the ME patients developed slight dysphonia, 10 developed medium grade dysphonia and three developed severe dysphonia. Seven of the CO2 laser patients developed slight dysphonia, seven developed medium grade dysphonia and six developed severe dysphonia. No statistically significant differences were observed on comparing the grade of dysphonia with patient age, T stage, type of cordectomy or surgical device. We consider the ME to be a useful and inexpensive alternative to CO2 laser.

Adult↗

Cognitive impairment in patients with multiple sclerosis using the Brief Repeatable Battery-Neuropsychology test.

AIMS: To assess the cognitive impairment of multiple sclerosis (MS) patients using the Brief Repeatable Battery-Neuropsychology (BRB-N) test. METHODS: The performance of 59 patients with MS in the BRB-N test was assessed and compared with 152 matched healthy controls (HC). RESULTS: In most tests, MS patients performed worse than controls. Age and educational level strongly influenced the performance of the subjects. The Symbol Digit Modality Test (SDMT) best correlated with the other individual tests and contributed most to the general BRB-N factor. Furthermore, a correlation between physical disability and performance in some BRB-N tests was observed. Indeed, patients with progressive MS and greater physical disability performed worse in some tests than less disabled patients with relapsing MS. By creating a global BRB-N Z score, we found that patients generally performed 0.7 standard deviation (SD) below the level of controls. We obtained cut-off values stratified by age and education to determinate cognitive impairment in MS patients. CONCLUSIONS: Our data show that cognitive impairment is prevalent amongst MS patients, and that a single cognitive measurement might be useful for monitoring patients during the progression of this illness.

Adolescent↗

Aging affects but does not eliminate the enzymatic antioxidative response to hypoxia/reoxygenation in cerebral cortex.

The effect of aging on basal and hypoxia/reoxygenation levels of both oxidative stress (protein carbonyl and TBARS) and antioxidative-enzyme activity (Cu/Zn-SOD; Mn-SOD; Catalase, CAT; Se-independent and Se-dependent glutathione peroxidase, GPX; glutathione transferase, GST and glutathione reductase, GR) has been studied in the cerebral cortex of adult and old rats. Oxidative stress markers increased with aging and show an age-dependent post-hypoxic response. Moreover, aging caused either no change (GST, GR and CAT) or an increase (Se-GPX, Cu/Zn-SOD, Mn-SOD) in the basal activity of the enzymes analysed. Only Se-independent GPX activity decreases. However, we detected an age-dependent response of SODs to the hypoxic injury. The early and sustained Cu/Zn-SOD activity rise in adult animals became late and weak in aged animals. Meanwhile, aging slowed the Mn-SOD post-hypoxic response although this activity was consistently higher in aged rats. Aging eliminated the post-hypoxic CAT response, but, perhaps offset by increased GPX activity, did not affect the GST response and slightly reduced post-hypoxic GR activity. In conclusion, aging rise basal ROS production, does not diminish or even increase the antioxidative-enzyme activity, and may slow but does not usually eliminate the enzymatic antioxidant response to the increased post-hypoxic ROS generation.

Aging↗

Constitutive nitric oxide synthases are responsible for the nitric oxide production in the ischemic aged cerebral cortex.

Aged brain shows reduced biological plasticity to meet emergency conditions such as ischemia, a process in which nitric oxide (NO) and apoptosis have been shown to play important roles. Using a model of transient global ischemia, we have analyzed the NO system and the p53, bax and bcl-2 response in the cerebral cortex of aged rats. Although immediately after ischemia the NO level is maintained, the reperfusion period increases NO concentrations together with the following: (i) greater bulk-protein nitration mainly due to a 50-kDa immunoreactive band; (ii) an increase in p53 protein; and (iii) an up-regulation of Bax together with a down-regulation of Bcl-2. These results match up with induced endothelial nitric oxide synthase expression immediately after ischemia and in neuronal nitric oxide synthase with the reperfusion. However, inducible nitric oxide synthase was not altered with ischemia/reperfusion. Altogether, these data suggest that NO production in cerebral cortex of aged ischemic animals is due to the constitutive NO synthase isoforms. This response is accompanied by the increased expression of pro-apoptotic proteins.

Aging↗

The influence of cellular seeding density in the microencapsulation of hybridoma cells.

The aim of this study was to assess the influence of different seeding densities on the function of hybridoma cells (clone 1B5, IgG 2alpha) producing an anti-angiogenic monoclonal antibody (mAb), microencapsulated using a high-voltage electrostatic field. Viable cells were microencapsulated in alginate/poly-L-lysine/alginate (APA) capsules and maintained in tissue culture. Cellular growth rates, production and release of mAb from the capsules were assessed. This study shows that hybridoma cells survive, proliferate and remain functionally competent for over one month in vitro after microencapsulation in APA capsules generated in an electrostatic field. However, the cell seeding density had to be at least 10(7) cells/ml for the microencapsulated cells to be viable and to produce and release mAb through the capsule membrane. The maximum monoclonal antibody concentration in this culture was 29.1 microg/ml by day 17, with a tendency to increase, but capsule breakage impeded the follow-up of this determination.

Alginates↗

Upregulation of endothelial nitric oxide synthase maintains nitric oxide production in the cerebellum of thioacetamide cirrhotic rats.

This study examines the expression and cellular distribution pattern of nitric oxide synthase (NOS) isoforms, nitrotyrosine-derived complexes, and the nitric oxide (NO) production in the cerebellum of rats with cirrhosis induced by thioacetamide (TAA). The results showed local changes in the tissue distribution pattern of the NOS isoforms and nitrated proteins in the cerebellum of these animals. Particularly, eNOS immunoreactivity in perivascular glial cells of the white matter was detected only in TAA-treated animals. In addition, although neither neuronal NOS (nNOS) nor inducible NOS (iNOS) cerebellar protein levels appeared to be affected, the endothelial NOS (eNOS) isoform significantly increased its expression, and NO production slightly augmented in TAA-treated rats. These NOS/NO changes may contribute differently to the evolution of the hepatic disease either by maintaining the guanosine monophosphate-NO signal transduction pathways and the physiological cerebellar functions or by inducing oxidative stress and cell damage. This model gives rise to the hypothesis that the upregulation of the eNOS maintains the physiological production of NO, while the iNOS is silenced and the nNOS remains unchanged. The differential NOS-distribution and expression pattern may be one of the mechanisms involved to balance cerebellar NO production in order to minimize TAA toxic injury. These data help elucidate the role of the NOS/NO system in the development and progress of hepatic encephalopathy associated with TAA cirrhosis.

Animals↗

Orally administered tryptophan and experimental type 2 diabetes.

There is a link between diabetes and oxidative stress. Hyperglycaemia leads to free radical generation and alterations of endogenous antioxidants. Our aim is to study the effect of orally administered L-tryptophan (TRP), the melatonin precursor, an endogenous antioxidant, on circulating levels of glycaemia, insulin and melatonin, and on the superoxide dismutase and catalase antioxidant systems in non-diabetic (ND) and type 2 diabetic (n5-STZ) male Wistar rats. At 19:30 every day for 15 days, TRP (125 mg/kg body weight) was administered orally. At 09:00 every two days the glycaemia was measured and every day the intake of food and water was recorded. At the beginning and end of treatment (at 09:00; 21:00; 02:00) plasma insulin and melatonin levels were measured, and (at 09:00) the enzymatic activities of catalase and superoxide dismutase (SOD) in erythrocytes were also measured. Glycaemia values were greater (p < 0.01) in n5-STZ rats than in ND rats, while insulin levels were lower (p < 0.05) at all times studied and these parameters were not altered by the TRP administration. Melatonin levels at 02:00 were lower in n5-STZ than in ND rats (p < 0.05). The TRP administration did not modify the circulating melatonin levels in ND rats, but raised (p < 0.01) the levels at 02:00 in the treated n5-STZ group. In ND rats after TRP administration there was a decline in catalase activity (p < 0.05), while in n5-STZ rats there was a rise (p < 0.01) at the end of treatment. However, there were no significant changes in SOD activity. There was increased food intake (g/day) in the treated n5-STZ group (p < 0.01). In conclusion, the oral administration of TRP did not modify glycaemia or insulinaemia levels, but raised melatonin levels in diabetic rats at 02:00, lowered catalase activity in ND rats but raised it in n5-STZ rats, and increased food intake in n5-STZ rats.

Administration, Oral↗

Exendin-4 dose-dependently stimulates somatostatin and insulin secretion in perfused rat pancreas.

We have investigated the effect of exendin-4, a GLP-1 analogue, on somatostatin and insulin secretion in perfused rat pancreas. At constant glucose concentration within the type 2 diabetic range (9 mM), exendin-4 stimulated somatostatin and insulin secretion in a dose-dependent manner. Dose-response curves were sigmoidal (R (2) = 0.9954 and R (2) = 0.9973, respectively; p < 0.01) and the EC (50) was 4.3 nM for somatostatin secretion and 1.4 nM for insulin secretion. Exendin-4 stimulated somatostatin output at low (3.2 mM), normal (5.5 mM) and high (9 mM) glucose concentrations, while the insulinotropic effect of exendin-4 was not found at low glucose levels. On the other hand, exendin-4 potentiated somatostatin and insulin responses to an increase in perfusate glucose levels, and to arginine and carbachol. Finally, the insulinotropic effect of exendin-4 was maintained in the absence of a somatostatin response as induced by cysteamine pretreatment, indicating a direct effect of exendin-4 on the B-cell. In summary, exendin-4 behaves as a general stimulatory agent of both insulin and somatostatin release in the perfused rat pancreas. Given that exendin-4 has also been shown to increase gastric somatostatin secretion, it is tempting to speculate that exendin-4 might behave as a general stimulator of D-cell function in other tissues, a point worthy of further investigation.

Animals↗

Findings of intravascular ultrasound during acute stent thrombosis.

OBJECTIVE: To evaluate the potential role of intravascular ultrasound (IVUS) in evaluating patients experiencing an episode of acute stent thrombosis. DESIGN AND SETTING: Prospective observational study in a cardiac catheterisation laboratory in a university teaching hospital. PATIENTS AND INTERVENTIONS: IVUS was used to examine 12 patients undergoing coronary interventions for stent thrombosis to gain further mechanistic insights and to guide treatment. IVUS studies were obtained before and after intervention with a motorised pullback device. MAIN OUTCOME MEASURES: Qualitative and volumetric IVUS analyses. RESULTS: Angiographically, 10 patients had occluded vessels and two patients had intraluminal filling defects within the stent. IVUS showed an occlusive thrombus in all patients. Thrombus volume was 90 (77) mm3, which was 51 (21)% of total stent volume. There was evidence of severe stent underexpansion in most patients and no patient fulfilled standard criteria for optimal stent implantation. Stent malapposition was detected in four patients, edge dissections were seen in two patients, and significant inflow-outflow disease was present in 11 patients. During interventions IVUS findings led to the use of higher pressures or larger balloons than those used during initial stenting in 10 patients. In addition, four patients required additional stenting, whereas a thrombectomy device alone was selected for one patient. After the procedure final minimum stent area (7.1 (2.1) v 5.3 (2) mm2, p < 0.005) and stent expansion (83.2 (17) v 62.1 (15)%, p < 0.005) improved compared with pre-interventional values. However, residual lining thrombus was still visualised in eight patients (25 (19) mm3, accounting for a 17% of final stent volume). CONCLUSIONS: IVUS provides an attractive technique to characterise fully the pattern of stent thrombosis, to identify readily the underlying mechanical predisposing factors, and to guide repeated coronary interventions.

Acute Disease↗

Testicular torsion and its effects on the spermatogenic cycle in the contralateral testis of the rat.

The aim of the present study was to evaluate the effects of unilateral testicular torsion on the contralateral testis with respect to the stages of the cycle of the seminiferous epithelium (CSE). Fifty-five male Wistar rats, 60 days old, were used. The animals were divided into 11 groups. Groups 1-5 were subjected to unilateral testicular torsion from 3 to 48 h, followed by detorsion. Groups 6-10 had unilateral orchiectomies after unilateral testicular torsion for 3 to 48 h. Animals constituting group 11 served as the control sham-operated group. All animals were killed after 2 months. The percentage of affected tubules (tubules showing pathological changes) in the contralateral testis was estimated based on the CSE stages. In the torsion/detorsion group, the percentage of affected tubules was significantly greater (58.6%) than in torsion/orchiectomy group (48.0%). Stages VI-XI of the spermatogenic cycle were the most affected when compared with the rest of the stages in each experimental group (P <0.05). These results show that stages VI-XI of the spermatogenic cycle, the stages associated with low antioxidant capacities, are the most sensitive to the effects of testicular torsion on the contralateral testis.

Animals↗

Effects of bosentan on neointimal response following coronary angioplasty.

BACKGROUND: Endothelins are important vasoconstrictors and cellular-growth promoters. ETA-specific antagonists have been shown to reduce neointimal response to injury in some experimental angioplasty models. However, there is little information on the effects of dual ETA/ETB receptor blockers, such as bosentan, on neointimal proliferation following experimental coronary angioplasty. MATERIALS AND METHODS: Coronary injury was achieved by directional atherectomy in the left anterior descending artery of 20 pigs. Animals were randomly assigned to receive a daily dose of oral bosentan (30 mg kg-1) (group I, n = 10) or no treatment (group II, n = 10). At 4 weeks, arteries were processed for histomorphometry and endothelin characterization. RESULTS: Vessel injury score was similar among the two groups. Overall, a linear correlation was found between injury and neointimal development (r = 0.57, P = 0.01). This correlation had a lower slope in group I compared with group II (P < 0.001), indicating a smaller amount of neointimal development for a similar degree of injury in bosentan-treated animals. Multivariate regression showed that neointimal response was reduced by oral treatment with bosentan (beta: -0.59 mm2, 95% CI: -1.11/-0.06 mm2). In addition, immunostaining revealed fewer positive endothelin areas in group I arteries. CONCLUSIONS: Oral treatment with bosentan reduces neointimal development following coronary angioplasty in this experimental model.

Administration, Oral↗

Morning cortisol production in coronary heart disease patients.

BACKGROUND: The circadian cycle of the endogenous anti-inflammatory system (EAIS) is characterized by a morning increase in cortisol production. Circulating interleukin-6 (IL-6) activates the EAIS. A circadian variation in the onset of myocardial infarction, sudden death, stable angina (SA) and unstable angina (UA) has been reported. The aim of this study was to determine morning cortisol production in coronary heart disease (CHD) patients. MATERIALS AND METHODS: Serum cortisol and IL-6 were measured in 129 patients with either SA (n = 65) or UA (n = 64) and 40 healthy volunteers. Blood samples were taken between 9 : 00 h and 12 : 00 h. The upper normal range of cortisol (25 microg dL-1) was used as a reference to classify patients. RESULTS: Forty-eight patients had elevated cortisol levels (ECL) (32.5 +/- 5.4 microg dL-1), while 81 patients had normal cortisol levels (NCL) (15.7 +/- 5.9 microg dL-1). In NCL patients, IL-6 levels (26.6 pg mL-1, ranged from 0.2 to 183.7) were significantly higher (P < 0.004) than in ECL patients (9.70 pg mL-1, range 0.07-56.5). Forty-eight patients with UA belonged to the NCL group of patients, while only 16 UA patients belonged to the ECL group (chi(2) = 0.000). Thirty-two patients with SA belonged to the ECL group, and 33 to the NCL group (chi(2) = 0.08). CONCLUSIONS: Patients with 'inappropriately' normal morning cortisol production had high IL-6 levels. 'Inappropriately' normal cortisol, detected in 75% of UA and 50% of SA patients, may be insufficient for limiting inflammation. These findings have novel clinical implications and suggest new therapeutic approaches in the treatment of these patients.

Aged↗

Ebstein's anomaly, atrial paralysis and atrio-ventricular block: an uncommon association.

We report here the case of a 22-year-old female patient with an incomplete Ebstein's anomaly, complete heart block and atrial standstill. Atrial paralysis associated with Ebstein's anomaly is the most important feature, since there is a report of familial Ebstein's anomaly associated with atrial standstill but isolated cases have not been described. The patient presented with atypical chest pain and a symptomatic bradycardia of 37 beats per minute. A VVIR pacemaker was implanted. She has subsequently been symptom free.

Adult↗

Characteristics of porous nickel-titanium alloys for medical applications.

We investigate the behavior of NiTi porous alloys, possessing the property of shape memory, by using different characterization methods XPS, Auger, DSC and SEM. The study mainly focuses on the determination of porosity, surface characteristics and the phase transformation. In the case of porous material the biomechanical compatibility is closely related to the internal structure and porosity distribution. To describe appropriately the influence of the properties of NiTi on the memory shape, two types of materials provided by different sources has been analyzed. Despite the fact that both materials present different pores size, they exhibit an open and interconnected porosity. Our measurements show that the temperature of the inception of the martensite-austenite phase transition occurs at 60 degrees C, which is by 20 degrees C greater than the body temperature. Moreover, we show that the surface characteristics can be greatly influenced by heat treatment. Furthermore, we observe that the R-phase occurs only for one of the used materials after its heat treatment. The correlation between the composition and the other characteristics measured has been found.

Alloys↗

Synthesis of 2,3-disubstituted pyrrolidines and piperidines via one-pot oxidative decarboxylation-beta-iodination of amino acids.

A new synthesis of 2,3-disubstituted pyrrolidines and piperidines is described. This mild procedure is based on the one-pot oxidative decarboxylation-beta-iodination of alpha-amino acid carbamates or amides. The iodine is introduced at the previously unfunctionalized 3-position. Different substituents can be introduced at C-2, e.g., hydroxy, alkoxy, allyl, alkyl, etc. A trans relationship between the C-2 and C-3 substituents is exclusively obtained. The influence of the solvent and the ring size of the starting amino acid are studied, as well as the nature of the protecting group on the nitrogen. The stereoselectivity of the reaction was also studied using chiral methyl (2S,4S)-4-acetyloxyproline-1-carboxylate (8). The products obtained can be manipulated to give bicyclic systems present in many natural products. By using the tandem decarboxylation-iodination-alkylation reaction, 2-substituted-3-iodopyrrolidines are formed, which are precursors of 2-substituted-2,5-dihydropyrrols.

Amino Acids↗

Stirrer tank: an appropriate technology to immobilize the CB.Hep-1 monoclonal antibody for immunoaffinity purification.

The CB.Hep-1 monoclonal antibody was coupled to CNBr-activated Sepharose CL 4B at three different immobilization scales for purification of recombinant hepatitis B surface antigen. Standard laboratory apparatus to obtain immunosorbents of 1 l (scale I) and 3 l (scale II) as well as a stirrer tank to prepare 6 l immunosorbents (scale III) were used. The binding capacity at scale III was 2- and 1.5-fold higher with respect to the scales II and I, while a reduction in the ligand leakage of 5- and 2-folds was observed. Immunosorbents from scale II showed a significantly reduced adsorption, and an increased ligand leakage. Differences in the coupling efficiency were not observed. Antigen purity eluted from the immunosorbents was always above 85%.

Antibodies, Monoclonal↗