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Biomedical subjects

R Rodríguez

Publications and source records attributed to R Rodríguez.

At least 19 recordsLinked to original sources

Diphenylpropionic acids as new AT1 selective angiotensin II antagonists.

The synthesis and pharmacological evaluation of a new series of potent AT1 selective diphenylpropionic acid nonpeptide angiotensin II receptor antagonists are reported. The new compounds were evaluated for in vitro AT1 (rat liver) and AT2 (rat adrenal) binding affinity as well as for in vivo inhibition of angiotensin II-induced increase in mean arterial blood pressure in pithed rats. Unsaturation of the diphenylpropionic acids as well as substitution or replacement by alkyl groups of the pendant phenyl ring resulted in a decrease of potency. On the other hand, the presence of small alkyl groups in the alpha-position to the carboxylic acid was important for activity, with one of the resultant diastereoisomers (R*,R*) being ca. 10-fold more active than the other (R*,S*). Oral evaluation of the most active compounds in a furosemide-treated sodium-depleted rat model showed that compound 36g (UR-7198) reduced blood pressure dose dependently. This compound showed in vitro and iv potencies similar to that of the reference compound losartan but faster onset of action and somewhat greater oral activity, presumably due to its improved bioavailability.

Administration, Oral

Expression in Escherichia coli of Sin a 1, the major allergen from mustard.

Sin a 1, the major yellow mustard allergen, is a seed storage protein that belongs to the 2S albumin family. It is composed of two disulfide-bonded polypeptide chains. The cloning of this allergen has been carried out by means of the polymerase chain reaction using non-degenerate oligonucleotides encoding the N-terminal and C-terminal regions of the mature protein as primers. Five genomic nucleotide sequences have been analyzed, encoding both mature polypeptide chains linked by the internal processed fragment. The sequence data show the existence of microheterogeneities at ten positions, demonstrating the polymorphism exhibited by the natural protein. One of the genomic clones was expressed in Escherichia coli by fusion to glutathione S-transferase from Schistosoma japonicum. The resulting chimeric protein was purified by affinity chromatography on a glutathione-Sepharose 4B matrix, and digested with thrombin to release the recombinant allergen. The recombinant Sin a 1 is recognized by rabbit polyclonal and mouse monoclonal antisera raised against natural Sin a 1, as well as by the IgE of mustard-sensitive human sera. In addition, recombinant Sin a 1 possesses a high resistance to trypsin digestion, like the native mustard allergen.

Allergens

Cross-reactivity between the major allergen from olive pollen and unrelated glycoproteins: evidence of an epitope in the glycan moiety of the allergen.

Ole e 1, the major allergen from olive pollen, is a glycoprotein containing a single Asn-linked glycan moiety. Rabbit antiserum against this protein has been obtained; and its immunologic cross-reactivities in Western blotting with ascorbate oxidase, horseradish peroxidase, bromelain, ovalbumin, and honeybee venom phospholipase A2 have been studied. Ascorbate oxidase, peroxidase, and bromelain are recognized by the Ole e 1 antiserum. When these three proteins are deglycosylated by periodate treatment, such an immunologic reaction does not occur. The relative affinities of these proteins have been analyzed by direct and inhibition ELISA experiments. A commercially available antibody against horseradish peroxidase has also been considered in these studies. This antibody reacts with Ole e 1 but not with the periodate-deglycosylated allergen. Horseradish peroxidase, bromelain, and ascorbate oxidase are recognized by the IgE of sera from patients who are hypersensitive to olive tree pollen. This binding is also abolished by periodate treatment. The results are interpreted in terms of the presence of an epitope in the carbohydrate moiety of Ole e 1, which would contain a xylose involved in recognition by both IgE and IgG antibodies.

Allergens

[Diet and migraine].

Some foods in our diet can spark off migraine attacks in susceptible individuals. Some foods can bring an attack on through an allergic reaction. A certain number such as citrus fruits, tea, coffee, pork, chocolate, milk, nuts, vegetables and cola drinks have been cited as possible allergens associated with migraine. This mechanism has however been criticized: an improvement in symptoms by eliminating some food(s) from our diet does not necessarily mean an immunologically based allergic reaction. The high IgE incidence rate is not greater in such patients than in the population at large. Other allergic reactions unrelated to diet may also be associated with migraine attacks. On the other hand substances in food may be the cause of modifications in vascular tone and bring migraine on in those so prone. Among such substances are tyramine, phenylalanine, phenolic flavonoids, alcohol, food additives (sodium nitrate, monosodium glutamate, aspartame) and caffeine. Another recognized trigger for migraine is hypoglycemia. Such foods as chocolate, cheese, citrus fruits, bananas, nuts, 'cured' meats, dairy products, cereals, beans, hot dogs, pizza, food additives (sodium nitrate, monosodium glutamate in Chinese restaurant food, aspartame as a sweetener), coffee, tea, cola drinks, alcoholic drinks such as red wine, beer or whisky distilled in copper stills, all may bring on a migraine attack. For every patient we have to assess which foodstuffs are involved in the attack (not necessarily produced by consuming the product concerned) in order to try to avoid their consumptions as a means of prophylaxis for migraine.

Diet

[Description of 31 pediatric cases of infection caused by human Parvovirus B 19].

FUNDAMENTALS: [corrected] Human Parvovirus B19 has been identified as the etiological agent implicated in several clinical forms of disease. The aim of this study was to define the clinical aspects observed in the children with human parvovirus infection in our hospital. METHODS: A retrospective study was done in 31 pediatric cases observed in our hospital from January-92 to July-94; all had positive IgM against Parvovirus (determined by enzymoinmunoanalysis). RESULTS: The most frequent signs and symptoms were fever in 66.6% of the cases and skin findings in 48%, manifested as typical infectious erythema in 26% and polimorphic nonspecific exanthema in the rest. There were variable blood manifestations, observed in 11 children (35%): Immune Thrombocytopenic purpura, Chronic anemia in immunocompromised hosts, bone marrow erithrophagocytosis and hemolytic crises in non-hemolytic anemia patients. The abnormal blood findings were mostly observed in children with compromised immunity. Articular disease was presented in four children (12%). Long lasting fever was observed in only one case. CONCLUSIONS: In our sample the diversity of clinical forms of presentation of Parvovirus B19 infection is well documented as it is reported by several authors. Although other studies as polymerase chain reaction (PCR), nucleic acid hybridization, direct visualization of the virus or its particles, or viral antigen detection are desirable to confirm the serologic studies.

Adolescent

[3 year survival in patients hospitalized for acute cerebrovascular disorders].

For three years we studied the mortality and functional situation of all patients admitted in 1991 to the Neurology Service suffering from acute stroke with the exception of subarachnoid haemorrhage cases. We analyzed the cause of death whether directly related to the initial illness or not. Out of 134 patients admitted for acute stroke, 48 (41.02% of the 117 patients examined after excluding 17 whom we did not obtain complete information from) had died after three years. The main causes of death were directly related to acute stroke (37.5%) and pneumonia (37.5%). Death occurred mainly in the first month (79.16% of deaths). Predictive variables for mortality directly related to acute stroke during the first month include severe weakness, brain haemorrhage, dysphasia and earlier incidence of acute stroke. Variables related to higher mortality rate due to other causes in the first month were dysphasia, age and angina antecedents, whereas earlier incidence of acute stroke was associated with a lesser mortality rate for these causes, as distinct from acute stroke itself. Greater levels of weakness and sphincteral incontinence are the best predictive signs of dependency functional situation at the end of the first month and, along with diabetes, after one and three years.

Acute Disease

Antineutrophil cytoplasmic antibodies in relatives of patients with inflammatory bowel disease.

BACKGROUND: The occurrence of antineutrophil cytoplasmic antibodies (ANCA) has been reported more frequently than expected in healthy first-degree relatives of patients with ulcerative colitis, suggesting that these antibodies may represent a subclinical marker of genetic disease susceptibility. AIM: To determine the prevalence of ANCA in unaffected first-degree relatives of inflammatory bowel disease patients in a Spanish population. METHODS: Three hundred and seventy sera obtained from 80 patients with inflammatory bowel disease (55 ulcerative colitis, 25 Crohn's disease), 217 unaffected first-degree relatives (157 from ulcerative colitis and 60 from Crohn's disease patients), 62 healthy controls, and 11 celiac disease patients were tested using an indirect immunofluorescence assay. RESULTS: Antibodies were detected in 64% of patients with ulcerative colitis but in only 12.5% of patients with Crohn's disease. ANCA were seldom present in their unaffected first-degree relatives (4.6%), control subjects (1.6%), and celiac disease patients (0%). CONCLUSIONS: In the Spanish population studied, antineutrophil cytoplasmic antibodies occur more commonly in ulcerative colitis than in Crohn's disease, as reported in other Caucasian populations. Moreover, their presence is not increased in their first-degree relatives. These findings indicate that ANCA are not a subclinical marker of genetic susceptibility to inflammatory bowel disease in this population.

Adult

[Sclerotherapy of post-renal transplantation lymphocele with percutaneous instillation of amidotrizoate].

Incidence of post-renal transplant (RT) lymphocele varies between 0.6% to 41% depending on the author. Therapeutical management of these entities is controversial. (Open or laparoscopic) surgical marsupialization of the peritoneal cavity, percutaneous drainage, and percutaneous sclerosis with povidone-iodine are all valid options to treat post-RT lymphocele. This paper presents two cases of symptomatic post-RT lymphocele not suitable for laparoscopic treatment, which were resolved by intracavitary instillation of Sodium Amidotrizoate 76%. The first case had been previously treated with povidone-iodine with no resolution, also maintaining a 500 ml/24h deficit. In the second case, instillation with Sodium Amidotrizoate 76% was considered first choice approach. In both instances the lymphocele deficit ceased with instillation intervals of 6 and 14 days, respectively. In brief, percutaneous sclerosis with Amidotrizoate can be a valid alternative for the treatment of post-RT lymphocele.

Adult

[Effect of the local anesthetic on visceral pain in cesarean sections done under intradural anesthesia].

OBJECTIVES: To evaluate the influence of local anesthetic on the incidence and severity of visceral pain during cesarean section performed under subarachnoid anesthesia. PATIENTS AND METHOD: This was a randomized double blind study of 90 parturients undergoing scheduled or emergency cesareans. The women were distributed among three groups according to local anesthetic used: 2% isobaric mepivacaine in group 1, 0.5% hyperbaric bupivacaine in group 2, and 0.5% isobaric bupivacaine with adrenalin in group 3. The total anesthetic dose was selected based on height, and pain was defined as silent and dull, or a sensation of pressure that was poorly defined, diffuse or referred to another area and accompanied or not by nausea and/or vomiting. Pain was assessed on a visual analog scale at various moments during surgery. Other variables recorded were metameric level of blockade, hemodynamic function and presence of nausea and/or vomiting. RESULTS: One patient in each group was excluded. The incidences of visceral pain and 95% confidence intervals were as follows: 38% (23-56%) in group 1 and 10% (3.5-25%) in groups 2 and 3 (p = 0.002). The metameric level of blockade differed significantly among the groups. The highest level (T1-5) was reached in group 1 but level was the most consistent (T3-5) in group 2. Systolic arterial pressures in all groups were significantly lower than baseline levels 5 min after puncture and the decrease was greatest in group 3. The highest incidence (p = 0.01) of nausea and/or vomiting occurred in the isobaric bupivacaine group. CONCLUSION: Use of hyperbaric bupivacaine offers advantages over the other techniques, as it assures more consistent attainment of metameric level, an incidence of visceral pain that is lower than that of isobaric mepivacaine, and fewer hemodynamic repercussions than isobaric bupivacaine with vasoconstrictor.

Adult

Concanavalin A- and wheat germ agglutinin-conjugated lectins as a tool for the identification of multiple N-glycosylation sites in heterologous protein expressed in yeast.

We report here a methodology that allows the identification of glycosylation sites by a combination of protein enzymatic digestion, glycopeptide separation on a reverse-phase HPLC column, and further recognition in a dot-blot system using concanavalin A-horseradish peroxidase. Wheat germ agglutinin-horseradish peroxidase is used as the recognition system for peptides generated after proteolytic digestion of endoglycosidase H deglycosylated protein. Glycosylation sites were confirmed by automatic Edman degradation and fast atom bombardment mass spectrometry. This methodology was applied to a model glycoprotein, alpha-amylase from Bacillus licheniformis, which is unglycosylated in its natural host and appears highly glycosylated when expressed in the methylotrophic yeast Pichia pastoris.

Amino Acid Sequence

Flagelliform or coronata glands of Nephila clavipes.

The flagelliform or coronata glands of the orb-web spider, Nephila clavipes, have been studied and compared to other silk-producing glands from the organism. The glands, which produce silk for the double filament of the core thread in the sticky spiral, exhibit three distinct morphological areas: tail, sac, and duct. Electrophoretic separation of the solubilized contents of the glands yields an uppermost diffuse band of high molecular size, preceded by a stepladder of well-defined peptides, which have been shown to be products of discontinuous translation in three other sets of glands. The luminal contents do not migrate as a discrete and well-defined band as those of the other glands, but rather as a diffuse area, typical of glycosylated proteins. Fibroin synthesis is stimulated by the mechanical depletion of the organism's stored silks, as in other Nephila glands, judged by the increased intensity of the bands and also by the structural alterations seen in cross sections of the glands' tails.

Animals

Involvement of nitric oxide in bone marrow-derived natural suppressor activity. Its dependence on IFN-gamma.

Bone marrow (BM)-derived natural suppressor (NS) cells are strong inhibitors of lymphoproliferative responses. In this study we have assessed the involvement of nitric oxide (NO) in BM-derived NS activity, as detected in cocultures of BM and spleen cells stimulated with B cell (LPS) or T cell (Con A) mitogens. The results indicate that NS activity is readily inhibited by NG-monomethyl-L-arginine, a competitive inhibitor of NO synthase, or N-acetylcysteine, a free radical-scavenging thiol compound. High amounts of nitrite, a stable end product of NO, are detected only in supernatants of Con A- or LPS-stimulated spleen cells cocultured with BM cells enriched in NS activity (Fr3 cells). These amounts (15 to 55 microM) are strongly antiproliferative for both Con A and LPS responses, as was established with a nitrite curve made with a NO donor (sodium nitroprusside). Fr3 cells cultured alone release large quantities of NO and express inducible NO synthase (iNOS) mRNA upon LPS stimulation, but require spleen cells in cultures stimulated with Con A. Anti-IFN-gamma-neutralizing Abs blocked both NO production and NS activity, irrespective of the mitogen used; yet, only exogenous IFN-gamma is unable to promote successful NO production by Fr3 cells, but does induce detectable iNOS mRNA expression in these cells. Taken together the results indicate that: 1) NO is the major mediator of BM-derived NS activity; 2) BM cells enriched in NS activity produce large amounts of NO through an IFN-gamma-dependent iNOS induction.

Acetylcysteine

[Drug prescriptions in general medicine practice].

OBJECTIVE: To find the origin of pharmacological prescriptions written in the primary care ambit, the effect of training on the prescribers and the influence of the organisational structure of the centres where they work on the quality of the drugs prescribed. DESIGN: Observational study of a crossover type. SETTING: Two health centres and two consulting-rooms in Areas 11 and 12, Valencia. MEASUREMENTS AND MAIN RESULTS: The sample calculated corresponded to 664 prescriptions per centre. The origin of the prescription differed, depending on the model, so that in the consulting-rooms the origin of 55% of prescriptions was specialist care, whereas in the health centres this percentage went down to 31%. There were significant differences (p < 0.0001) in the quality of prescription in different organisational structures, but there were no significant differences among professionals with different training. CONCLUSIONS: A high percentage of pharmacological prescriptions have their origin in specialist care. Prescription quality is conditioned basically by the organisational model and is appreciably better in health centres.

Cross-Over Studies

Biotin supplementation affects lymphocyte carboxylases and plasma biotin in severe protein-energy malnutrition.

We studied the effect of a supplement of biotin (10 mg/d) or a placebo under double-blind conditions on plasma biotin concentrations and lymphocyte propionyl CoA carboxylase (PCC) and pyruvate carboxylase (PC) in 22 children with severe protein-energy malnutrition (PEM) (5 with kwashiorkor, 10 with marasmus, and 7 "sugar babies"). There were significant differences between the malnourished and control subjects only for PCC, although not among the three PEM types. Six of the patients had both PC and PCC activities below the lowest of the normal control subjects; there was no correlation between biotin concentrations and carboxylase activities in individual patients. In response to biotin supplementation, the greatest change in lymphocyte carboxylase activities was detected in patients who had abnormally decreased initial carboxylase activities, but the response was not related to initial plasma biotin concentration. These results indicate that these enzyme deficiencies are the result of a nutritionally determined biotin deficiency, that carboxylases and especially PCC are better indicators of the biotin status in individual patients than is the plasma biotin concentration, and that in some malnourished patients biotin deficiency may be rate-limiting in their nutritional homeostasis.

Biotin

[Vascular complications in renal transplantation].

Between the years 1979 and 1992 we a total of 479 renal transplants (RT) were performed. In 62 patients (12.9%) there were some clinically significant vascular complications. These have consisted of: 10 cases of arterial thrombosis (2%); 10 cases of venous thrombosis (2%); 5 cases of arterial and venous thrombosis (1%); 31 cases of arterial stenosis (6.5%); and 6 cases of acute haemorrhage originated at the vascular anastomosis level (1.2%). In all those cases with arterial or venous thrombosis, or both, it was necessary to perform transplantation. The arterial stenosis cases were treated with antihypertensive agents in 13 patients; with endoluminal percutaneous angioplasty (EPA) in other 13 patients and with surgery in 5. Both arterial stenosis and complications from their treatment resulted in 5 transplantations. In all cases with early post-surgical haemorrhage originated at the vascular anastomosis level, a surgical review and suture of bleeding site was performed. A total of 31 grafts (6.5%) were lost as a result of vascular complications.

Adolescent

[Comparative study of single-dose intradural anesthesia and continuous intradural anesthesia with or without fentanyl].

OBJECTIVE: To compare the hemodynamic effects, level of anesthetic blockade and advantages of single-dose versus continuous intrathecal anesthesia with hyperbaric bupivacaine with and without fentanyl. PATIENTS AND METHOD: Prospective study in 45 patients under 65 who were scheduled for elective surgery of the lower abdomen, randomly divided into 3 groups. Group 1 and 2 received continuous intrathecal anesthesia with 10 mg hyperbaric bupivacaine; group 2 also received 25 mcg fentanyl. Patients in group 3 were given a single intrathecal dose of 15 mg hyperbaric bupivacaine. Mean arterial pressure and heart rate were recorded at baseline and 10, 20 and 30 minutes after the start of anesthesia. The level of block achieved was recorded after 10, 30 and 60 minutes. Hemodynamic changes, differences in blockade and side effects were analyzed. RESULTS: Hemodynamic changes were greater in group 2 (fentanyl) than in groups 1 and 3 (p < 0.05), with group 3 showing the greatest degree of hemodynamic stability. Level of blockade was always higher in group 2, with significant differences at 30 min (p < 0.05). Seven and 5 reinjections by catheter were necessary in groups 1 and 2, respectively. Two patients in group 3 required general anesthesia when blockade was inadequate. Apart from pruritus in group 2 (40%), no side effects due to anesthesia were observed. CONCLUSIONS: A single dose intrathecal anesthesia, produces less hemodynamic changes than a continuous intrathecal block. Nevertheless, continuous intrathecal block, allows the maintenance of the block as long as required. The association of fentanyl enhances the hemodynamic changes with no other beneficial effects.

Adult

[Comparison of changes in plasma concentrations of ACTH and beta-endorphin in cholecystectomy under general anesthesia and general plus epidural anesthesia].

OBJECTIVE: To study neuroendocrine response during cholecystectomy under general anesthesia with fentanyl and under general anesthesia with nitrous oxide plus thoracic epidural block, by determining plasma levels of ACTH and beta-endorphin. PATIENTS AND METHODS: This was a prospective study of 2 randomly chosen groups of 7 patients each who were undergoing cholecystectomy. One group received general anesthesia with fentanyl at initial doses of 10 micrograms/kg-1 followed by perfusion of 5 micrograms.kg-1.h-1. The other group received general anesthesia with 60% nitrous oxide in oxygen combined with bupivacaine 0.5% for thoracic epidural blockade. Plasma levels of ACTH and beta-endorphin were determined at the following moments: A, upon arrival in the operating theater; B, after anesthetic induction and intubation; C, after incision; D, 30 minutes after start of surgery; E, after surgery but before extubation, and F, after arrival in the recovery room. Also recorded were mean arterial pressure and heart rate. RESULTS: In both groups we found significantly higher levels of beta-endorphin throughout surgery. The increase was greater, however, in the group receiving combined anesthesia at moments D (p = 0.008) and E (p = 0.008). ACTH levels rose significantly during surgery (p = 0.004) in the combined anesthesia group, whereas there was only a slight increase in the group receiving only general anesthesia (p = NS). beta-endorphin levels increased proportionally more than ACTH levels during combined anesthesia. Hemodynamic stability was acceptable in both groups. CONCLUSION: General anesthesia with fentanyl at the dose used in this study was more effective that combined anesthesia in mitigating the release of ACTH and beta-endorphin during cholecystectomy.

Adrenocorticotropic Hormone

[HIV infection declines among intravenous drug addicts in Barcelona: 1987-1993].

BACKGROUND: The evolution of the prevalence of HIV infection in intravenous drug addicts who initiate hospital detoxication was analyzed. METHODS: Six hundred fifty intravenous drug addicts (535 males, 115 females) were analyzed for HIV and surveyed in regard to demographic variables and the use of drugs over a period of 7 years (1987-1993): age, sex, year of initiation of intravenous drug addiction, length of the habit and year of admission. RESULTS: Most of the subjects were men (82%) with a mean age of 19.7 years at the time of initiation to the use of i.v. drugs and an age of 25.9 years on admission to the unit. The mean time of i.v. drug addiction at admission was 74 months. The characteristics of the patients according to the year of admission were homogeneous in regard to age, length of drug addiction and male/female ratio. More than 50% of the subjects had initiated the use of i.v. drugs during the first half of the last decade. The global prevalence of HIV infection was of 66.3% with no differences being observed between sexes. The frequency of infection was shown to have globally decreased from 1987 to 1993 (p = 0.06) although the rates of HIV infection in women did not significantly modify (p = 0.08) in contrast to that of men (p = 0.05). CONCLUSIONS: The epidemia of HIV infection in intravenous drug addicts may have entered into remission following a decade characterized by a spread in the use of heroin and great diffusion of the disease.

Adult