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Biomedical subjects

C Alvarez

Publications and source records attributed to C Alvarez.

At least 37 records · Page 2Linked to original sources

Glucose uptake and glucose transporter proteins in skeletal muscle from undernourished rats.

Undernutrition in rats impairs secretion of insulin but maintains glucose normotolerance, because muscle tissue presents an increased insulin-induced glucose uptake. We studied glucose transporters in gastrocnemius muscles from food-restricted and control anesthetized rats under basal and euglycemic hyperinsulinemic conditions. Muscle membranes were prepared by subcellular fractionation in sucrose gradients. Insulin-induced glucose uptake, estimated by a 2-deoxyglucose technique, was increased 4- and 12-fold in control and food-restricted rats, respectively. Muscle insulin receptor was increased, but phosphotyrosine-associated phosphatidylinositol 3-kinase activity stimulated by insulin was lower in undernourished rats, whereas insulin receptor substrate-1 content remained unaltered. The main glucose transporter in the muscle, GLUT-4, was severely reduced albeit more efficiently translocated in response to insulin in food-deprived rats. GLUT-1, GLUT-3, and GLUT-5, minor isoforms in skeletal muscle, were found increased in food-deprived rats. The rise in these minor glucose carriers, as well as the improvement in GLUT-4 recruitment, is probably insufficient to account for the insulin-induced increase in the uptake of glucose in undernourished rats, thereby suggesting possible changes in other steps required for glucose metabolism.

Animals↗

Effects of long-term treatment with antipsychotics on serum leptin levels.

BACKGROUND: Abnormal regulation of the adipocyte-derived hormone leptin could play a role in body weight gain induced by antipsychotics. AIMS: To study the effects of long-term antipsychotic treatment on leptin levels in patients with schizophrenia. METHOD: Serum leptin levels were determined in 59 out-patients with chronic schizophrenia and in the same number of healthy subjects controlled by gender, age and body mass index. RESULTS: Leptin levels did not differ between patients and controls. Leptin levels in patients with schizophrenia correlated with weight gain, even after controlling for current weight, but did not show any association with clinical variables. Antipsychotic class tended to exert different effects over leptin levels (among atypicals, olanzapine induced a greater increase). CONCLUSIONS: Elevation of leptin levels induced by chronic antipsychotic treatment can be attributed to weight gain, but other mechanisms could be involved.

Adult↗

Regulation of IGF-I and -II by insulin in primary cultures of fetal rat hepatocytes.

During perinatal development, insulin and nutrients, rather than GH, regulate the IGF system. A selective primary culture of fetal rat hepatocytes has been established in our laboratory to elucidate the molecular mechanism of action of the above regulatory factors on IGF-I and -II gene expression during the late fetal period of the rat. In this model we have previously reported a regulatory role for glucose on IGF-I and -II synthesis and secretion. In the same experimental model, we now report that doses of insulin (0.1-5 microM) within the physiological range in rat fetuses during the last stages of gestation evoke an increase of IGF-I and -II mRNA abundance. Insulin regulated in a parallel manner IGF peptide secretion, and an excellent correlation was observed between IGF-I and -II mRNA and IGF-I and -II peptide levels in the conditioned media in response to the hormone. Finally, the insulin-induced rise in IGF-I and -II mRNA was not mediated by stimulation of gene transcription but by increased transcript stability. The results support the hypothesis that insulin plays a major role in IGF regulation at immature stages of development.

Animals↗

Effect of thyroxine administration on the IGF/IGF binding protein system in neonatal and adult thyroidectomized rats.

The effects of different doses of thyroxine (T(4)) delivered by injection or s.c. pellet implantation on alterations of the IGF/IGF binding protein (IGFBP) system were studied in neonatal and adult thyroidectomized (Tx) rats. Body weight, blood glucose, plasma insulin, TSH and GH and pituitary GH content, as well as serum IGF-I, IGF-II, IGFBP-1, -2 and -3 and their liver mRNA expression were assayed. Pellet implantation with the smaller dose of T(4) (1.5 microg/100 g body weight (b.w.) per day) in Tx neonatal rats decreased serum IGF-I, -II and the 30 kDa complex of IGFBPs (IGFBP-1 and -2), and increased serum IGFBP-3. Only the larger dose of T(4) (3 microg/100 g b.w. per day) recovered liver mRNA expression of IGF-I and ensured euthyroid status as shown by the normalized levels of plasma TSH. The rapid increase of body weight and serum GH after T(4) administration indicated a high sensitivity to T(4) during the neonatal period. Serum and liver mRNA expression of IGFs and plasma insulin and GH recovered in adult Tx rats after pellet implantation of 1.75 microg/100 g b.w. per day throughout 10 days. The continuous replacement of T(4) by pellet seems to be the most suitable method for thyroid rehabilitation. A very good correlation was found between insulin and IGF-II in Tx neonates treated with T(4) but not between insulin and IGF-I in Tx adults. IGFBP-2 seems to be up-regulated by T(4) deprivation in neonatal and adult rats. Finally, a good correlation as well as a partial correlation were found between IGFs and thyroid hormones in both neonatal and adult Tx populations, suggesting a direct effect in vivo of T(4) on the hepatic secretion of IGFs, as previously suggested in vitro.

Analysis of Variance↗

[High prevalence of subclinical thyroidal disease among individuals attended in health control].

BACKGROUND: There is no information about the prevalence of thyroidal diseases in the general Chilean population. AIM: To assess the prevalence of thyroidal diseases in individuals attended in occupational health examinations. SUBJECTS AND METHODS: Four hundred seventy two individuals were examined between 1998 and 1999. In all, serum levels of thyroid hormones, TSH and anti thyroidal antibodies (anti microsomal, anti thyroid peroxidase and anti thyroglobulin) were measured. RESULTS: Forty four subjects were excluded from the study due to an incomplete medical record and 18 due to a personal history of thyroidal disease. Abnormal serum levels of thyroid hormones or TSH were detected in 28 subjects (6.8%). Four (1%) had hypothyroidism, 23 a subclinical hypothyroidism (5.6%) and one (0.2%) had hyperthyroidism. In 87 subjects (21.2%) at least one of the antibodies was positive. Positive anti thyroid antibodies were found in 14 of 28 subjects (50%) with abnormal thyroid hormone levels, compared with 73 of 382 subjects (19.1%) with normal thyroid hormone levels. Thyroid dysfunction was twice as frequent in women than in men. CONCLUSIONS: In this sample, a 6.8% prevalence of abnormal thyroid function tests was detected.

Adolescent↗

[Computer analysis of respiratory sounds in bronchial obstruction evaluation in small children that do not collaborate with spirometry tests].

BACKGROUND: There are changes in inspiratory breath sound intensity in patients with airway obstruction. Airway narrowing may change sound spectral characteristics. AIM: To define the characteristics of lung sounds at standardized air flow during methacholine challenge and to compare acoustic changes with transcutaneous oxygen tension (PtcO2) during induced airway narrowing. PATIENTS AND METHODS: Forty asthmatic children (20 male) aged 5.2 +/- 1 years and 40 normal children (18 male), aged 5.6 +/- 1 years were studied. All patients were free of respiratory tract infections one month before the study. A methacholine challenge from 0.06 to 8 mg/ml was performed; the test was ended when a fall in PtcO2 of > 20% from baseline was observed or if the final concentration was reached. Subjects breathed through a pneumotachograph aiming at flows of 0.4 to 0.6 l/s. Respiratory sounds were recorded using contact sensors at the suprasternal notch and at the posterior right lower lobe. From average spectra, power at low (100-200 Hz = P1) and high frequencies (400-2000 = P2) was calculated. Frequencies below which 50% (F50) and 99% (SEF90) of the spectral power between 100 and 2000 Hz was contained, were also calculated. RESULTS: In asthmatics, the metacholine concentration at which a 20% fall in PtcO2 was observed, was lower than in normal children (p < 0.05). There was an increase in P1 (p < 0.01) and a reduction in P2 (p < 0.01) during inspiration, in subjects that experienced a 20% reduction in PtcO2. Also, there was an increase in F50 and SEF99 during inspiration in lung sounds, but not over the trachea. CONCLUSIONS: Lung sounds analysis can be useful for the assessment of airway reactivity in asthmatic children.

Asthma↗

[Pleural effusion and complicated empyema in children. Evolution and prognostic factors].

BACKGROUND: Complicated pleural empyema has a torpid and longer clinical evolution, requiring in some patients surgical management. The predictive factors for surgical treatment are not well known. AIM: To search for clinical, laboratory or radiological predictors for the requirement of surgical treatment in pediatric patients with empyema. PATIENTS AND METHODS: A retrospective review of the charts of 108 patients hospitalized for pneumonia plus pleural effusion at the Pediatric Service of the Catholic University Hospital between January 1985 and July 2000. RESULTS: Eighty one patients had complete radiological evaluation and pleural fluid biochemical analysis. Forty nine (60%) fulfilled the criteria for empyema and 32 (40%) for an exudate. Thirteen patients with empyema required surgery and 36 were treated medically. The mean age was 3 years (range 9 months-6 years) for the surgically treated and 4 years (range 12 months-14 years) for the non-surgical group. The male/female ratio was 5:1 in the surgical group and 1:1 for the non-surgical group. Pleural fluid cultures were positive in 21 of 79 patients. Streptococcus pneumonia was the most frequently isolated agent. No significant differences were found between groups for the average days of fever prior to the diagnosis or total days of fever, days of hospital stay, pleural fluid pH (6.8 and 7.0 respectively) and glucose (21 and 31 mg/dl respectively). No differences were either observed for pleural fluid risk factors (pH < 7 and glucose < 20 mgdl), the presence of extensive pleural effusions, pleural loculations or bands on pleural ultrasonography and positive Gram stain or cultures in the pleural fluid. Surgical patients required oxygen for more days than medical patients (7.7 and 5.1 days; p = 0.037). CONCLUSIONS: This study failed to find predictive clinical, radiological or pleural fluid parameters, for the requirement of surgical treatment of empyema.

Adolescent↗

The p115-interactive proteins GM130 and giantin participate in endoplasmic reticulum-Golgi traffic.

The transport factor p115 is essential for endoplasmic reticulum (ER) to Golgi traffic. P115 interacts with two Golgi proteins, GM130 and giantin, suggesting that they might also participate in ER-Golgi traffic. Here, we show that peptides containing the GM130 or the giantin p115 binding domain and anti-GM130 and anti-giantin antibodies inhibit transport of vesicular stomatitis virus (VSV)-G protein to a mannosidase II-containing Golgi compartment. To determine whether p115, GM130, and giantin act together or sequentially during transport, we compared kinetics of traffic inhibition. Anti-p115, anti-GM130, and anti-giantin antibodies inhibited transport at temporally distinct steps, with the p115-requiring step before the GM130-requiring stage, and both preceding the giantin-requiring stage. Examination of the distribution of the arrested VSV-G protein showed that anti-p115 antibodies inhibited transport at the level of vesicular-tubular clusters, whereas anti-GM130 and anti-giantin antibodies inhibited after the VSV-G protein moved to the Golgi complex. Our results provide the first evidence that GM130 and giantin are required for the delivery of a cargo protein to the mannosidase II-containing Golgi compartment. These data are most consistent with a model where transport from the ER to the cis/medial-Golgi compartments requires the action of p115, GM130, and giantin in a sequential rather than coordinate mechanism.

Antibodies↗

Higher levels of serum copper in schizophrenic patients treated with depot neuroleptics.

The findings of previous research on the status of trace elements in patients with schizophrenia have been controversial. We studied 62 outpatients with a DSM-IV diagnosis of schizophrenia, and compared them with sex- and age-matched healthy controls. Serum copper levels were significantly higher in schizophrenic patients (mean 117.4 microg/dl; S.D. 23.4) than in healthy controls (105.6+/-27.9). Those patients on treatment with depot neuroleptics had higher copper levels. Zinc levels did not differ between patients and healthy controls. Altered levels of trace elements in schizophrenic patients may be a consequence of antipsychotic treatment.

Adult↗

Prevalence of genotypic resistance to nucleoside analogues and protease inhibitors in Spain. The ERASE-2 Study Group.

OBJECTIVE: To examine the prevalence of resistance mutations to nucleoside reverse transcriptase inhibitors (NRTI) and protease inhibitors (PI) in a representative HIV-1 population in Spain. METHODS: A cross-sectional study was conducted including 601 HIV-infected patients who attended 20 Spanish hospitals in June 1998. Drug resistant mutations were examined using hybridization line probe assays (LiPA). The 6 bp insert at position 69 and the codon 75 mutant were examined by sequencing analysis in specimens lacking reactivity to 69/70 and 74 bands on LiPA, respectively. RESULTS: Primary resistance to NRTI was recognized in nine out of 52 (17%) naive individuals, whereas primary resistance to PI was found in seven out of 126 (6%) PI-naïve patients. The codons most frequently involved in NRTI resistance were at positions 70 (66%), 184 (44%), 215 (33%), and 41 (11%), whereas the most common PI resistance mutation was at codon 82 (6/7 subjects). In pre-treated patients, the overall prevalence of resistant genotypes was 72.9% for NRTI and 27.2% for PI. The most frequent NRTI mutations occurred at codons 184 (38.5%), 215 (30.1%), and 41 (22.5%), whereas the most frequent PI mutations in pre-treated subjects were found at positions 82 (15.8%) and 84 (11.4%). Overall, patients who began triple combinations as initial therapy showed a lower number of key resistance mutations than those who began highly active antiretroviral therapy (HAART) after being exposed to NRTI for a period of time (mean number of mutations, 0.1 versus 1.8, P< 0.05). Codon 75 mutant was found in three out of 387 patients (0.7%), whereas no insertions at codon 69 were recognized. CONCLUSION: The prevalence of primary genotypic resistance to NRTI and PI in Spain was 17% and 6%, respectively. Zidovudine, lamivudine, indinavir and ritonavir were the drugs most frequently affected. These data support the use of resistance testing prior to the introduction of first-line antiretroviral therapies in Spain. Among pre-treated subjects, drug resistance genotypes were less prevalent in those who began HAART as initial therapy.

Adult↗

Complicated enterocutaneous fistulas: failure of octreotide to improve healing.

Octreotide has been promoted as a potential aid during closure of enterocutaneous fistulas (ECFs) on the basis of clinical and experimental evidence that it can reduce gastrointestinal secretions. We retrospectively reviewed the records of patients admitted with ECF to our tertiary referral center to ascertain whether use of octreotide affected fistula duration, length of hospitalization, closure rate, and morbidity. Of 60 patients diagnosed and treated for ECF over a 4-year period, 13 underwent a therapeutic trial with octreotide. Thirteen patients from the group who did not receive octreotide were matched by cause, location, and output of the fistula, age, and primary diagnosis to the treatment group. Octreotide was administered in therapeutic dosage for a mean course of 57 +/- 29 days, resulting in a substantial acute decrease (84.7 +/- 4.8%) in fistula output. Prolonged therapy nevertheless failed to affect the outcome parameters studied, particularly fistula duration, spontaneous closure rate, and length of hospitalization. There was a significantly higher incidence of septic and thrombotic complications associated with octreotide use. In this patient population with complicated ECFs, use of octreotide showed no benefit and was associated with increased morbidity.

Cutaneous Fistula↗

Technique and early results of outpatient laparoscopic mesh onlay repair of ventral hernias.

BACKGROUND: This report describes the technique and early results of a simple outpatient laparoscopic ventral hernia repair. METHODS: Data were gathered prospectively for all laparoscopic ventral hernia repairs from January 1996 to December 1997 at a 228-bed hospital. Prolene mesh was stapled to the peritoneal surface of the abdominal wall, leaving sac in situ and mesh uncovered. Patients were seen by the operating surgeon within 2 months, and by an impartial surgeon (J.S.) after 3 to 14 months (average, 7 months; median, 6 months). RESULTS: Repairs involved 44 hernias with orifice sizes 2 to 20 cm in diameter, and an average area of 20 cm(2). Of these 44 hernias, 36 were postoperative and 8 primary. Furthermore, 20% were recurrent hernias. There were four conversions. The outpatient rate was 98%, with one readmission for ileus. The early recurrence rate was 5%. CONCLUSIONS: Laparoscopic mesh onlay repair is a safe, easy, and effective procedure with minimal discomfort and a low early recurrence rate that can be performed safely on an outpatient basis.

Adult↗

The road to ambulatory laparoscopic management of perforated appendicitis.

BACKGROUND: This study examines the contribution of increased laparoscopic skills to ambulatory management of perforated appendicitis. METHODS: All 38 perforated appendicitides from 151 laparoscopic appendectomies done by one surgeon were studied and ambulatory management (discharge less than 24 hours after surgery) of the last 18 perforations reported. RESULTS: Over 4 years, rate of attempted laparoscopic appendectomy rose from 67% to 100% for perforations. Conversion rate fell from 100% to 22%. Ileus and pain control were not problems for most laparoscopic perforations, so by the end of 1997, experience suggested these patients might be discharged within 24 hours. Ambulatory rate was 57% (conversions excluded). There were no readmissions for wound infections or postoperative abdominal abscesses. CONCLUSIONS: Increasing laparoscopic skills allows laparoscopic treatment of complicated appendicitis with a low conversion rate and no infectious complications. Over one half of these patients can be managed as outpatients without jeopardy to outcome.

Adult↗

Modification of acquired immunity in BALB/c mice by aztreonam.

Recent studies have suggested that antibiotics may act as biological response modifiers. In this study we investigated the effect of aztreonam, a monobactam antibiotic, on different parameters of acquired immunity in BALB/c mice. Different dosages of aztreonam injected into mice induced an increase in the lymphoproliferative response to specific mitogens and in the production of interleukin-2 by splenic cells, as well as a decreased response of this immune population to sheep erythrocytes lower total blood cell counts and a lower percentage of monocytes than in untreated mice. These results show a modulatory action of aztreonam on different immune parameters, which is independent of its antimicrobial activity and that could be of interest in human therapy.

Animals↗

CCR5 (chemokine receptor-5) DNA-polymorphism influences the severity of rheumatoid arthritis.

Chemokines are critical for the inflammatory process in autoimmune diseases such as rheumatoid arthritis (RA). The chemokine receptor-5 (CCR5) mediates chemotaxis by CC-chemokines and is expressed by lymphocytes with the Th1 phenotype and monocyte/macrophages. A 32 bp deletion in the CCR5 (CCR5-delta 32 allele) abolishes receptor expression in homozygotes, while CCR5-delta 32 carriers would express less receptor than wild-type homozygotes. This polymorphism is related to the resistance to HIV-1 infection and progression towards AIDS. We hypothesized that the CCR5-delta 32 allele may modulate the severity of disease in RA. A total of 160 RA-patients (71 and 89 with severe and non-severe phenotypes, respectively) and 500 healthy individuals from the same Caucasian population (Asturias, northern Spain) were genotyped. Carriers of the CCR5-delta 32 allele were at a significantly higher frequency (P = 0.012) in non-severe compared to severe patients (17% vs 4%). Our results suggest that the CCR5-delta 32 polymorphism is a genetic marker related to the severity of RA.

Arthritis, Rheumatoid↗

The membrane transport factor p115 recycles only between homologous compartments in intact heterokaryons.

Cytosolic proteins that participate in membrane traffic are assumed to be recruited from the cytosol onto specific membrane sites where they perform their function, and then released into cytosol before rebinding to catalyze another round of transport. To examine whether the ER to Golgi transport factor p115 recycles through release into a cytosolic pool, we formed heterokaryons between rat NRK and simian COS-7 cells and examined the dynamics of rat p115 transfer from the rat to the simian portion of the heterokaryon. The heterokaryons shared a common cytosolic pool, as shown by the efficient relocation of a cytosolic green fluorescent protein (GFP) from the COS-7 to the NRK part of the heterokaryon. Unexpectedly, even 24 h after cell fusion, rat p115 did not redistribute to the COS-7 part of the heterokaryon. This was not due to the inability of the rat p115 to associate with simian membranes since rat p115 expressed in COS-7 cells was efficiently targeted to and associated with simian Golgi complex. Furthermore, rat p115 associated with heterologous simian membranes after the NRK and COS-7 Golgi fused into a single chimeric structure. Our results indicate that p115 is not freely diffusible in intact cells and might remain tethered to membranes throughout its life cycle. These findings suggest that p115, and perhaps other cytosolic proteins involved in membrane traffic, recycle not by being released into cytosol, but in association with recycling membranes.

Animals↗

The origin of the Jingwei gene and the complex modular structure of its parental gene, yellow emperor, in Drosophila melanogaster.

Jingwei (jgw) is the first gene found to be of sufficiently recent origin in Drosophila to offer insights into the origin of a gene. While its chimerical gene structure was partially resolved as including a retrosequence of alcohol dehydrogenase (ADH:), the structure of its non-ADH: parental gene, the donor of the N-terminal domain of jgw, is unclear. We characterized this non-ADH: parental locus, yellow emperor (ymp), by cloning it, mapping it onto the polytene chromosomes, sequencing the entire locus, and examining its expression patterns in Drosophila melanogaster. We show that ymp is located in the 96-E region; the N-terminal domain of ymp has donated the non-ADH: portion of jgw via a duplication. The similar 5' portions of the gene and its regulatory sequences give rise to similar testis-specific expression patterns in ymp and jgw in Drosophila teissieri. Furthermore, between-species comparison of ymp revealed purifying selection in the protein sequence, suggesting a functional constraint in ymp. While the structure of ymp provides clear information for the molecular origin of the new gene jgw, it unexpectedly casts a new light on the concept of genes. We found, for the first time, that the single locus of the ymp gene encompasses three major molecular mechanisms determining structure of eukaryotic genes: (1) the 5' exons of ymp are involved in an exon-shuffling event that has created the portion recruited by jgw; (2) using alternative cleavage sites and alternative splicing sites, the 3' exon groups of ymp produce two proteins with nonhomologous C-terminal domains, both exclusively in the testis; and (3) in the opposite strand of the third intron of ymp is an essential gene, musashi (msi), which encodes an RNA-binding protein. The composite gene structure of ymp manifests the complexity of the gene concept, which should be considered in genomic research, e.g., gene finding.

Alternative Splicing↗

Effect of early dietary restriction on insulin action and secretion in the GK rat, a spontaneous model of NIDDM.

The availability of the Goto-Kakisaki (GK) rat model of non-insulin-dependent diabetes mellitus prompted us to test the effect of a limited period of undernutrition in previously diabetic young rats on their insulin secretion and insulin action during adult age. Four-week-old female GK rats were either food restricted (35% restriction, 15% protein diet) or protein and energy restricted (35% restriction, 5% protein diet) for 4 wk. Food restriction in the young GK rat lowered weight gain but did not aggravate basal hyperglycemia or glucose intolerance, despite a decrease in basal plasma insulin level. Furthermore, the insulin-mediated glucose uptake by peripheral tissues in the GK rat was clearly improved. We also found that food restriction, when it is coupled to overt protein deficiency in the young GK rat, altered weight gain more severely and slightly decreased basal hyperglycemia but conversely aggravated glucose tolerance. Improvement of basal hyperglycemia was related to repression of basal hepatic glucose hyperproduction, despite profound attenuation of basal plasma insulin level. Deterioration of tolerance to glucose was related to severe blunting of the residual glucose-induced insulin secretion. It is, however, likely that the important enhancement of the insulin-mediated glucose uptake helped to limit the deterioration of glucose tolerance.

Aging↗