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Biomedical subjects

M Moreno

Publications and source records attributed to M Moreno.

At least 37 records · Page 2Linked to original sources

Local and systemic immune responses to Echinococcus granulosus in experimentally infected dogs.

Local and systemic immune responses were studied in six dogs experimentally infected with the dog/sheep tapeworm Echinococcus granulosus. All dogs developed similar IgG antibody response to parasite antigens. In contrast, IgE and IgA responses differed widely. No relationship between IgA responses and parasite burden at the end of the infection were observed. Further, clear differences in the anti-parasite IgA response in serum as compared with specific IgA forming cells in mesenteric lymph nodes were observed within the same dog. An inverse association of anti-parasite IgE and parasite load seemed to be present, with the strongest IgE response in the one dog that had no worms in the intestine at the end of the experiment. No differences were observed in the numbers of intestinal mast cells and goblet cells among all infected dogs. However, the dog with no detectable parasite load had a marked reduction of detected mast cells in the submuscular and muscular layer of the mucosa. Our data give new insight into the immune response of dogs during E. granulosus infection and provide information that may be useful for the rational design of vaccines for the control of hydatid disease.

Animals↗

Compliance matching stent placement in the carotid artery of the swine promotes optimal blood flow and attenuates restenosis.

OBJECTIVES: We assessed the value of a gradient-compliant stent in an animal model. METHODS: Bilateral carotid arteries were stented with nitinol stents having variable-oversizing, variable-stiffness, and with (CMS, 10 animals) and without (SMART, four animals) compliance-matching endings. Angiography, hemodynamic, scanning-electron-microscopic and histological analyses were performed at 3-month. The protocol was completed in 14 among 19 swines. RESULTS: Transient (1-month) exaggerated recoil, attributable to stress-induced phasic inhibition of vasorelaxation, developed at CMS endings. At mid-term, all stents were endothelialized; CMS-stents, but not SMART-stents, were incorporated into walls (one-strut-thickness). Restenosis developed outside SMART-stents (cell migration+wall-compensatory enlargement) whereas CMS-stents elicited no or focalized cell-accumulations at endings that bulged vascular walls radially outward. SMART-stents were blood-flow neutral, whereas CMS-stents favored (higher-stiffness, higher-oversizing) or opposed (lower-stiffness, less-oversizing) carotid blood flow. CONCLUSIONS: Direct carotid stenting with stents having compliance-matched endings and specific requirements of stiffness and oversizing can optimize blood flow to the brain and restrict local restenosis.

Animals↗

Thermal AFM: a thermopile case study.

In this work, an atomic force microscope (AFM) with an integrated thermal sensor has been used to obtain the local spatial distribution of temperatures in a micromachined thermopile with submicron resolution. In this communication, we will show how the dimensional, structural and functional characteristics of a thermopile suits well with the requirements for AFM thermal imaging, and how a deeper insight of the thermopile operation can be gained with the aid of these advanced scanning probe-based tools.

Diagnostic Imaging↗

Development of a new disease-specific quality-of-life questionnaire to adults living with haemophilia.

A haemophilia-specific health-related quality-of-life questionnaire (named 'Hemofilia-QoL') was developed to assess quality-of-life in adults with haemophilia, and was psychometrically tested. Seventy-three interviews with haemophilia patients and health care professionals were used to generate the items included in the questionnaire, and expert ratings on the items formulated were used to screen them for potential omission. This was followed by psychometric testing in a sample of 35 patients. Preliminary psychometric testing of the revised questionnaire version, which contains 10 domains (physical health, physical role, joint damage, pain, treatment satisfaction, emotional role, mental health, social support), showed acceptable reliability (alpha = 0.94 for the Hemofilia-QoL total score) and validity, and this will be examined in a subsequent study with a larger patient sample.

Adolescent↗

Chagas' disease susceptibility/resistance: linkage disequilibrium analysis suggests epistasis between major histocompatibility complex and interleukin-10.

Association between the major histocompatibility complex (MHC) and the susceptibility/resistance to acquire Chagas' disease has been largely demonstrated. To study the role of candidate genes in this susceptibility/resistance to Chagas, we designed a population-genetic-based case-control approach (chagasic n = 104 and controls n = 60) and tested the presence of genotype and linkage disequilibrium on microsatellite loci establishing specific landmarks for the MHC, interleukin (IL)-2, IL-2Rbeta chain, IL-4, IL-10, and natural resistance-associated mactophage protein 1 (NRAMP1). After demonstrating no genetic stratification among cases and controls (F(st) were not different from 0), we found significant allelic differences among chagasic patients and controls at microsatellite locus D6S291 (MHC) and at the microsatellite pointing out the IL-10. At the MHC, we found significant differences between patients and controls in Hardy-Weinberg equilibrium-expected genotype proportions. Additionally, MHC II-locus-inferred haplotypes in chagasic patients exhibited strong significant departures from the expected proportions predicted by the second Mendelian law. The linkage disequilibrium pattern at MHC involves a region of approximately 10 cM. These results replicate previous analyses and suggest that presence of epistasis between MHC with humoral systems, such as IL-10, could be underlying the susceptibility/resistance to Chagas' disease.

Alleles↗

A population-based study on the incidence of inflammatory bowel disease in Oviedo (Northern Spain).

OBJECTIVE: to assess the incidence of inflammatory bowel disease in Oviedo (Northern Spain), and to describe the clinical features of new patients. PATIENTS AND METHODS: a prospective population-based study was made at the Health Area IV, Principality of Asturias (Oviedo, 312,324 inhabitants). All new diagnosed patients with inflammatory bowel disease were registered over a 2-year period. RESULTS: a total of 85 patients were included, 47 of these with ulcerative colitis (UC), 37 with Crohńs disease (CD), and 1 with undetermined colitis. The overall adjusted incidence rate of UC and CD per 105 inhabitants between 15-64 years was 9.1 (95% CI: 5-13.1) and 7.5 (95% CI: 3.8-11.2), respectively. The global male/female ratio was 0.9, without significant differences between both diseases. CD patients were younger than those with UC (33 +/- 15 years vs 45 +/- 20 years; p < 0.05). Mostly, CD patients were diagnosed at an age younger than 35 years (65%), while UC patients were diagnosed at an age between 25 and 64 years (81%). Disease extension in UC was proctitis in 11%, left-side colitis in 53% and extensive colitis in 36%. With respect to CD, the ileo-colonic form predominated (49%), followed by the ileal (40%) and colonic (11%) forms; an inflammatory, stenotic and fistulous pattern was seen in 54, 22 and 24% of patients, respectively. CONCLUSIONS: in our area, the incidence of CD is similar to that in other Northern European countries, while UC has a lower incidence. CD mainly affects young people, while UC predominates in middle-aged patients. At diagnosis, UC is predominantly localized, the ileo-colonic form and an inflammatory pattern being most frequent in CD patients.

Adolescent↗

Retreatment and maintenance therapy with infliximab in fistulizing Crohn's disease.

OBJECTIVES: Infliximab has clearly demonstrated its efficacy in the short-term treatment of fistulizing Crohn's disease. We present here the results of retreatment and long-term maintenance therapy. PATIENTS AND METHODS: Eighty one consecutive patients with active fistulizing Crohn's disease, in whom previous treatments had failed, were treated with infliximab. All patients received as the initial treatment of 5 mg/kg i.v. infusions (weeks 0, 2, and 6). Those patients who failed to respond after the initial cycle (group 1, n = 25), or those who relapsed after having responded (group 2, n = 13), received retreatment with three similar doses (weeks 0,2, and 6). Those who responded to retreatment were included in a long-term maintenance programme (n = 44), with repeated doses (5 mg/kg i.v. infusions) every eight weeks for 1-2 years. RESULTS: In the initial treatment 56% of the patients responded partially; this response being complete in 44%. In the retreatment, 28% of group 1 (non-responders) presented a complete response, compared to 77% in group 2 (relapsers) (p < 0.0001). In the maintenance treatment, the global response was 88% (39/44). The mean number of doses per patient was 4.4 +/- 2 (range 1-9) with a duration of 36 +/- 12 weeks (range 8-72). Adverse effects were not significantly increased in either treatment. CONCLUSIONS: Both retreatment and long-term maintenance therapy with infliximab, are highly effective and well tolerated in fistulizing Crohn's disease patients.

Adolescent↗

Comparison of the performance of the Gea extracorporeal knot with the Roeder extracorporeal knot and the classical knot.

BACKGROUND: Laparoscopy is useful to treat surgical diseases, yet tying sutures in the cavity is a challenge. A knot to secure tissue approximation, which would be hand-made, secure, simple, easy, quick, reliable, and extracorporeal without extra mechanical devices, was developed and named the Gea knot. METHODS: A comparative study of the Gea knot, the Roeder knot, and the classical surgical knot, as the gold standard, using polypropylene, silk, catgut, polyglycolic acid, and Polyglactin 910, all of them of 1-0 caliber, was performed in pigs. Measurements were time to perform, slippage, and breaking point which was measured with a manual digital tensiometer. RESULTS: The Gea knot was significantly faster statistically to perform than the Roeder knot and more resistant against rupture and slippage. The slippage rate was significantly lower statistically in the Gea knot than in the Roeder knot when Polyglactin 910 and polypropylene were used. CONCLUSION: The Gea knot is a good alternative for laparoscopic procedures.

Absorbable Implants↗

Thyroid hormone and uncoupling proteins.

Thyroid hormone (TH/T3) exerts many of its effects on energy metabolism by affecting gene transcription. However, although this is an important target for T3, only a limited number of T3-responsive genes have been identified and studied. Among these, the genes for uncoupling proteins (UCPs) have attracted the interest of scientists. Although the role of UCP1 seems quite well established, uncertainty surrounds the physiological function of the recently discovered UCP1 analogs, UCP2 and UCP3. The literature suggests that T3 affects both the expression and the activity of each of these UCPs but further studies are needed to establish whether the mechanisms activated by the hormone are the same. Recently, because of their larger range of expression, much attention has been devoted to UCP2 and UCP3. Most detailed studies on the involvement of these proteins as mediators of the effects of T3 on metabolism have focused on UCP3 because of its expression in skeletal muscle. T3 seems to be unique in having the ability to stimulate the expression and activity of UCP3 and this may be related to the capacity of T3 to activate the integrated biochemical processes linked to UCP activity, such as those related to fatty acids, coenzyme Q and free radicals.

Animals↗

Uncoupling proteins-2 and 3 influence obesity and inflammation in transgenic mice.

OBJECTIVE: To test the hypothesis that either uncoupling protein-2 UCP2 or UCP3 or both together influence obesity and inflammation in transgenic mice. DESIGN: We generated 12 lines of transgenic mice for both human UCP2 and 3 using native promoters from a human bacterial artificial chromosome (BAC) clone. The BAC expresses no genes other than UCP2 and 3. Mice used for experiments are N4 or higher of backcross to C57BL/6J (B6). Each experiment used transgenic mice and their nontransgenic littermates. RESULTS: Northern blots confirmed expression on human UCP2 in adipose and spleen, while human UCP3 expression was detectable in gastrocnemius muscle. Western blots demonstrated a four-fold increase of UCP2 protein in spleens of Line 32 transgenic animals. Heterozygous mice of four lines showing expression of human UCP2 in spleen were examined for obesity phenotypes. There were no significant differences between Lines 1 and 32, but female transgenics of both lines had significantly smaller femoral fat depots than the control (littermate) mice (P=0.015 and 0.005, respectively). In addition, total fat of transgenic females was significantly less in Line 1 (P=0.05) and almost significantly different in Line 32 (P=0.06). Male Line 1 mice were leaner (P=0.04) while male Line 32 mice were almost significantly leaner (P=0.06). Heterozygous mice of Lines 35 and 44 showed no significant differences from the nontransgenic littermate controls. Effects of the UCP2/UCP3 transgene on obesity in Line 32 mice were confirmed by crossing transgenic mice with the B6.Cg-Ay agouti obese mice. B6.Cg-Ay carrying the UCP2/UCP3 transgene from Line 32 were significantly leaner than nontransgenic B6.Cg-Ay mice. Line 32 UCP2/UCP3 transgenics showed increased hypothalamic Neuropeptide (NPY) levels and food intake, with reduced spontaneous physical activity. Transgenic baseline interleukin4 (IL-4) and interleukin6 (IL-6) levels were low with lower or later increases after endotoxin injection compared to wild-type littermates. Endotoxin-induced fever was also diminished in transgenic male animals. Low-density lipoprotein (LDL) cholesterol levels were significantly higher in both Line 1 and 32 transgenics (P=0.05 and 0.001, respectively) after they had been placed on a moderate fat-defined diet containing 32% of calories from fat for 5 weeks. CONCLUSION: Moderate overexpression of UCP2 and 3 reduced fat mass and increased LDL cholesterol in two independent lines of transgenic mice. Thus, the reduced fat mass cannot be due to insertional mutagenesis since virtually identical fat pad weights and masses were observed with the two independent lines. Line 32 mice also have altered inflammation and mitochondrial function. We conclude that UCP2 and/or 3 have small but significant effects on obesity in mice, and that their mechanism of action may include alterations of metabolic rate.

Adipose Tissue↗

Is thiopurine methyltransferase genetic polymorphism a major factor for withdrawal of azathioprine in rheumatoid arthritis patients?

OBJECTIVE: To determine whether the presence of thiopurine methyltransferase (TPMT) alleles associated with reduced or absent activity of thiopurine methyltransferase is a major factor for withdrawal of azathioprine (AZA) in rheumatoid arthritis (RA) patients. METHODS: The TPMT genotype, including the variable number of tandem repeats (VNTR) pattern in the 5' untranslated region, was analysed in 111 patients with long-standing RA. Azathioprine (AZA) therapy was used in 40 patients (36%) as a disease-modifying anti-rheumatic drug. RESULTS: Seven out of 111 RA patients (6.3%) were carriers of a mutant allele, TPMT3A (G(460)-->A, A(719)-->G) being the mutant allele observed most frequently. In the group of 40 AZA-treated patients, therapy was discontinued in six patients because of side-effects and in 26 patients because of lack of efficacy. Three patients presented moderate side-effects and were homozygous for the wild-type TPMT allele, whereas the remaining three patients, who developed gastrointestinal effects with severe nausea and vomiting, were TPMT3A carriers. CONCLUSION: In this observational study, the absence of response, probably due to the low-dose scheme used, was the major cause of AZA withdrawal in our series of RA patients. TPMT genotyping may allow the use of high doses of AZA in patients with normal TPMT alleles to improve the efficacy of this immunosuppressive drug. Our data support the relationship between gastrointestinal intolerance and thiopurine metabolic imbalance.

5' Untranslated Regions↗

Expression and regulation of scavenger receptor class B type I (SR-BI) in gall bladder epithelium.

BACKGROUND AND AIMS: Biliary lipid absorption by the gall bladder mucosa and the cholesterol content of the gall bladder wall appear to play a role in cholesterol gall stone formation. As the scavenger receptor class B type I (SR- BI) regulates cellular cholesterol uptake, we studied its expression in human and murine gall bladders, its regulation by increased biliary lipid content, and its role in gall stone formation. METHODS AND RESULTS: Using immunohistochemistry, SR-BI was found in the apical domain of human gall bladder epithelial cells. Immunoblotting of isolated membranes from gall bladder epithelial cells showed a specific signal for the 82 kDa SR-BI protein. In C57BL/6 mice, SR-BI was also found in the gall bladder epithelium. Using western blot analysis, an inverse relationship was observed between biliary cholesterol concentration and SR-BI expression in murine gall bladder mucosa. By comparing lithogenic diet fed wild-type and SR-BI deficient mice, gall bladder wall cholesterol content and gall stone formation were not found to be dependent on SR-BI expression. CONCLUSIONS: (i) SR-BI is expressed in both human and murine gall bladder epithelium; (ii) biliary cholesterol hypersecretion is associated with decreased gall bladder SR-BI expression in mice; and (iii) murine SR-BI is not essential in controlling gall bladder wall cholesterol content and gall stone formation during diet induced cholelithiasis.

Animals↗

Portable spectral Doppler echocardiographic device: overcoming limitations.

BACKGROUND: There is evidence that new portable echocardiographic devices are useful in evaluating heart anatomy and function, but a lack of Doppler modes has up to now been an important limitation in obtaining haemodynamic data. OBJECTIVES: To report the Doppler capabilities of a new hand held echocardiographic device. DESIGN: Blinded comparison of two types of echocardiography machine. SETTING: Tertiary care centre. PATIENTS: 98 consecutive patients were randomly imaged with the hand held device, with a standard platform as reference. OUTCOME MEASURES: Pulsed wave transmitral Doppler inflow tract velocities, deceleration time, and continuous wave Doppler measurements of aortic ejection and tricuspid regurgitation peak velocities were recorded. RESULTS: There was excellent agreement between the hand held device and standard echocardiography for the evaluation of diastolic E and A waves, E/A ratio, and deceleration time with pulsed wave Doppler (intraclass correlation coefficients of 0.97, 0.93, 0.90, and 0.78, respectively). In addition, good agreement was found between continuous wave Doppler measurements of aortic ejection and tricuspid regurgitation velocities (intraclass correlation coefficients of 0.96 and 0.80). However, there was a significant difference between patients with tricuspid regurgitation measured with the hand held device (25.5%) and by standard echocardiography (65.3%), resulting in misdiagnosis of eight patients with pronounced pulmonary hypertension. CONCLUSIONS: New hand held devices with Doppler capabilities overcome previous limitations in evaluating haemodynamic variables. With colour Doppler they are now suitable for the complete evaluation of valvar disease and diastolic function. However, important limitations remain in the evaluation of pulmonary pressures.

Aortic Valve Stenosis↗

Impression cytology of the conjunctival epithelium after antiglaucomatous treatment with latanoprost.

PURPOSE: To study nongoblet and goblet epithelial conjunctival cells after several treatment periods with latanoprost, a prostaglandin analogue. METHODS: Twelve patients (20 eyes) were studied before the onset of treatment and after 1, 3, and 6 months of latanoprost use. Impression cytology was carried out to analyze cellular density and morphologic parameters such as minimum and maximum diameter and area. RESULTS: Nongoblet epithelium cell density did not change over the treatment period. The density of goblet cells increased after 1 month of use, but returned to initial cell density after longer treatment periods. Nongoblet epithelial cells underwent a significant reduction in size after 1, 3, and 6 months of treatment. In addition, the minimum/maximum diameter ratio suggested that after 1 month there were some changes in shape (a slight elongation) when compared to cells of untreated patients. Nevertheless, after longer treatment periods, the cells regained their original shape. No changes in size were observed in goblet cells, except for a slight decrease in maximum diameter after 6 months of treatment, which suggests that the cells became more rounded. CONCLUSIONS: The density of nongoblet epithelial cells does not change after different treatment periods with latanoprost. However, their size decreases and after short treatment periods their shape also undergoes changes. The density of goblet cells increases after 1 month of treatment, but decreases again after longer periods. Their size does not undergo any modification, although there is a variation in shape after 6 months of treatment.

Antihypertensive Agents↗

[Antiretroviral therapy from 1996-2000].

A retrospective study was carried out from September 1996 to June 2000 and examined the antiretroviral therapies prescribed to HIV patients in whom the viral load had been determined. Triple therapy was the most frequently prescribed during the study and the annual percentage increased to 60% in the last semesters analyzed. Large variability in antiretroviral combinations was observed and depended on the clinical center and unit. The number of individuals who began viral-load monitoring before being treated with antiretroviral drugs showed a progressive increase.

Adolescent↗

Alendronate daily, weekly in conventional tablets and weekly in enteric tablets: preliminary study on the effects in bone turnover markers and incidence of side effects.

Bisphosphonates are now in the vanguard of osteoporosis treatment. Frequently, gastro-oesophageal symptoms are associated with these drugs. The objective of this study was to compare side effects and bone turnover markers in postmenopausal women who had received alendronate daily or weekly in tablets with or without enteric coating. We conducted a randomised, double-blind, 3-month trial. The trial involved 75 volunteers, aged 45-58 with moderate to severe osteopenia (T-score lower than -2 SD) assessed by quantitative ultrasound. Women were assigned randomly to receive: (a) alendronate 10mg/day: (b) alendronate 70 mg once a week: or (c) enteric alendronate 70 mg per week. We recorded side effects, C-telopeptide, osteocalcin and urine hydroxyproline at the start of the study and at 3 months. After 3 months, pyrosis (heartburn) was noted by seven women in group A (28%), three in group B (12%) and two in group C (8%); nausea: by one woman in group B; and headache by one patient in each group. C-telopeptide (A: 40.7%; B: 34.1% and C: 38.5%); hydroxyproline (A: 31.1%;B: 25.3% and C: 31.5%) and osteocalcin (A: 27.0%; B: 25.4% and C: 25.1%) decreased similarly in the three groups. Weekly intake of alendronate, whether conventional or enteric-coated; is associated with less heartburn and nausea. Enteric alendronate has a similar action to the conventional tablets on biochemical markers.

Administration, Oral↗

Skeletal muscle mitochondrial free-fatty-acid content and membrane potential sensitivity in different thyroid states: involvement of uncoupling protein-3 and adenine nucleotide translocase.

The effect of triiodothyronine (T3) on mitochondrial efficiency could be related to an increase in the concentrations of some proteins, such as uncoupling proteins (UCPs). Free fatty acids (FFA) seem to be a cofactor essential for the uncoupling activity of UCP3. In this paper, we report that the hypothyroidism-hyperthyroidism transition is accompanied by increases: (i) in the endogenous levels of mitochondrial FFA and (ii) in the sensitivity to FFA shown by the mitochondrial respiration rate and membrane potential, which correlated with the level of UCP3 protein. The level of the mRNA for adenine-nucleotide translocase-1 (ANT) was not affected by the thyroid state, while the ANT contribution to FFA-induced changes in mitochondrial uncoupling was low in the hypothyroid and euthyroid states but became more relevant in the hyperthyroid state at the highest concentration of FFA.

Adenine Nucleotide Translocator 1↗