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Biomedical subjects

J A Moreno

Publications and source records attributed to J A Moreno.

At least 19 recordsLinked to original sources

The SstI polymorphism of the apo C-III gene is associated with insulin sensitivity in young men.

AIMS/HYPOTHESIS: Insulin resistance is considered to be a risk factor for diabetes and coronary heart disease and is determined by the interaction between genetic and environmental factors. The SstI polymorphism in the apolipoprotein C-III gene has been related to the presence of different features of the insulin resistance syndrome. We investigate if this mutation influences the peripheral effect of insulin in healthy young subjects (30 men and 29 women) eating a westernised diet. METHODS: We investigated peripheral insulin sensitivity with the insulin suppression test after a 28-day westernised high-saturated fat diet (38% total fat and 18% saturated fat with 115 mg of cholesterol per 1000 Ju). RESULTS: Steady state plasma glucose values were lower in S1-S1 compared with S1-S2 men (p=0.018 by ANOVA), but not in women (p=0.723). CONCLUSION/INTERPRETATION: There was no difference between carriers and non-carriers of the S2 allele in relation to incidence and sensitivity; although on subgroup analysis there was an effect in men but not in women.

Adult↗

Cerivastatin improves insulin sensitivity and insulin secretion in early-state obese type 2 diabetes.

In a double-blind, placebo-controlled, randomized crossover study, 15 stable mild hyperglycemic patients without treatment and with features of metabolic syndrome were treated with cerivastatin (0.4 mg/day) or placebo for 3 months. The insulin sensitivity index during the euglycemic-hyperinsulinemic clamp (EHC; 5.4 mmol/l; 80 mU x m(-2) x min(-1)) was increased by cerivastatin treatment (66.39 +/- 3.9 nmol x lean body mass [LBM](-1) x min(-1) x pmol(-1) x l(-1)) as compared with placebo (58.37 +/- 3.69 nmol x LBM(-1) x min(-1) x pmol(-1) x l(- 1); P < 0.01) by 13.7%. Glucose oxidation during EHC was significantly higher with statin treatment (16.1 +/- 1.37 micromol x LBM(-1) x min(-1)) as compared with placebo (14.58 +/- 1.48 micromol x LBM(-1) x min(-1); P < 0.05). During hyperinsulinemia (approximately 800 pmol/l) in EHC steady-state, lipid oxidation was significantly decreased and respiratory quotient was significantly increased with statin treatment (0.33 +/- 0.05 mg x LBM(-1) x min(- 1), 0.94 +/- 0.01) as compared with placebo (0.48 +/- 0.06 mg x LBM(-1) x min(-1), 0.91 +/- 0.01; P < 0.01 and P < 0.05, respectively). During statin treatment, the first-phase insulin response increased from 2.07 +/- 0.28 to 2.82 +/- 0.38 pmol x l(-1) x pmol(-1) (P < 0.05). The second phase of insulin responses examined by C-peptide and insulin levels averaged during the hyperglycemic clamp (20 mmol/l) was unchanged. In conclusion, this study demonstrates that 0.4 mg cerivastatin therapy improves first-phase insulin secretion and increases insulin-mediated glucose uptake and respiratory quotient in the early state of obese type 2 diabetes.

Blood Glucose↗

Molecular detection of respiratory syncytial virus in postmortem lung tissue samples from Mexican children deceased with pneumonia.

BACKGROUND: Respiratory syncytial virus (RSV) is the major viral cause of severe respiratory infections in children younger than 2 years of age. Nevertheless there are not enough epidemiologic data about the role of RSV as a cause of infantile mortality from pneumonia, mainly in young children from developing countries Aim. To determine the frequency of RSV infection in lung tissue samples from Mexican children deceased with pneumonia, by reverse transcription (RT) and PCR. METHODS: Postmortem lung tissue samples from 98 children younger than 2 years of age who died of pneumonia during the period of 1989 to 1997 were studied. Paraffin was removed with xylene from 10-microm lung sections, the total RNA was extracted and complementary DNA was obtained by RT reaction. A nested PCR with the use of oligonucleotides specific for the F glycoprotein gene was developed. Samples negatives for RSV were tested for the absence of polymerase inhibitors and for complementary DNA integrity. RESULTS: Twenty-nine of the 98 (30%) children deceased with pneumonia were positive for RSV by RT-PCR; 8 were detected from 13 (62%) children with histopathologic diagnosis of viral pneumonia and 21 from 85 (25%) children with histopathologic diagnosis of bacterial pneumonia (P = 0.018). There was no significant difference in RSV infection according to age groups or seasonal pattern. CONCLUSIONS: RSV infection is frequent in Mexican children younger than 2 years of age who died of pneumonia. Although RSV was more common in viral pneumonia, mixed infections with RSV and bacterial pneumonia were also common.

Autopsy↗

Zinc uptake by human erythrocytes with and without serum albumins in the medium.

Different mechanisms of Zn uptake are present in mammalian cells. The variations in the Zn uptake by human erythrocytes in the absence and presence of albumins, bovine and human, as well as the differences of Zn uptake with and without 4-4'-diidothiocyanatostilbene-2,2'-disulfonic acid have been analyzed in this study. The results show a significantly greater rate of Zn uptake in the absence rather than in the presence of albumins in the extracellular medium and being significantly greater with bovine than with human serum albumin when the experiments were performed in media with equimolar concentrations of Zn. However, when comparing Zn uptake in a medium without albumin with similar free-Zn concentration to Zn ultrafiltrable (20%) of other one with albumin, a significantly greater Zn uptake on the latter was observed. The DIDS inhibition on Zn uptake is higher if the albumin is also present in the medium. These results suggest that in Zn uptake by erythrocytes the albumin directly or indirectly would be involved, facilitating the well-known processes of passive transport and anionic exchanger.

Albumins↗

Plant activation of aromatic amines mediated by cytochromes P450 and flavin-containing monooxygenases.

To know the mechanisms involved in the activation of promutagenic aromatic amines mediated by plants, we used Persea americana S117 system (S117) for the activation of 2-aminofluorene (2-AF) and m-phenylenediamine (m-PDA) in Ames assays. In these assays, the effect of the diphenylene iodonium (DPI), an inhibitor of flavin-containing monooxygenases (FMOs), of the 1-aminobenzotriazole (1-ABT), an inhibitor of cytochromes P450 (cyt-P450s) and of the methimazole, a high-affinity substrate for FMOs, was studied. The efficacy of both inhibitors and of the methimazole was verified to find that they did partially inhibit the mutagenesis of both aromatic amines, activated with rat liver S9. Similarly, both inhibitors and methimazole did produce a significant decrease in 2-AF and m-PDA mutagenesis, when the activation system was S117, indicating that, similar to what occurs in mammalian systems, plant FMOs and cyt-P450s can metabolize aromatic amines to mutagenic product(s). However, the affinity of both FMOs and cyt-P450s of plant for 2-AF and m-PDA was different. Data obtained indicate that the activities of plant FMOs must be the main enzymatic system of m-PDA activation while, in 2-AF activation, plant cyt-P450s have the most relevant activities. In addition, peroxidases of the S117 system must contribute to 2-AF activation and some isoforms of FMOs and/or cyt-P450s of the S117 system, uninhibited by the inhibitors used, must be the responsible for a partial activation of m-PDA.

Amines↗

Interferon alfa-2b plus ribavirin for chronic hepatitis C patients who have not responded to interferon monotherapy.

BACKGROUND: The role of combination therapy is poorly defined in chronic hepatitis C patients who are non-responders to interferon. AIM: To assess the efficacy, safety and tolerance of interferon alfa-2b plus ribavirin in chronic hepatitis C patients who do not respond to interferon monotherapy. METHODS: A total of 127 non-responder patients with chronic hepatitis C received 3 mU t.i.w. of interferon alfa-2b plus 1000-1200 mg ribavirin daily for 48 weeks. Effects of therapy were evaluated by serum aminotransferases and hepatitis C virus (HCV) RNA levels. RESULTS: Twenty-nine (23%) patients had an end-of-treatment response. Six months after treatment, 20 (16%) patients were sustained responders. Early loss of HCV RNA was the strongest predictor of a sustained response (P < 0.0001). Remission was also more frequent in patients with genotype 1b (P < 0.02), elevated alanine aminotransferase (P < 0.03) and low gamma glutamiltranspeptidase (P < 0.002). Treatment was discontinued in 21 (17%) patients: in 14 for intolerance and in seven due to side-effects. CONCLUSIONS: Combination therapy with interferon plus ribavirin produced a sustained response in 16% of chronic hepatitis C patients who were non-responders to interferon. This combination was safe and well tolerated.

Adult↗

Hypercoagulability state in hip and knee surgery: influence of ABO antigenic system and allogenic transfusion.

It is well know that people with blood group O have a lower risk for venous thromboembolic disease (VTED) than does the general population. Moreover blood transfusion has been identified as a risk factor for VTED in patients with major trauma. The aim of this work is to investigate the behaviour of several markers of hypercoagulability before and after substitutive surgery of hip and knee in order to evaluate the relationship between the plasmatic levels of these markers, the ABO antigenic system and the allogenic blood transfusion. The plasmatic levels of D dimer (D-D), thrombin-antithrombin complex (TAT), and fragment 1 + 2 of prothrombin (F1 + 2) have been determined by the ELISA method in 79 patients subject to substitutive surgery of hip or knee one day before and one day after surgery. The 41 patients with blood groups different from O had presurgical levels of F1 + 2 higher than those of group O (p = 0.004), while no differences could be found for D-D and TAT. The 28 patients who received allogenic blood presented higher levels of D-D one day after surgery than non-transfused patients (p = 0.043); the practice of transfusion did not modify significantly the levels of TAT and F1 + 2 after surgery. In accordance with these results we suggest that blood group and transfusion are risk factors for hypercoagulability, and therefore we advise for a restrictive policy of transfusion practice. New therapies such as aprotinin should be assayed in order to minimize blood loss.

ABO Blood-Group System↗

Hemorheological profile in chronic venous insufficiency after surgery.

In recent years, there have been rheological abnormalities reported in chronic venous insufficiency (CVI), mainly an increase of erythrocyte aggregability (EA), which probably take part in the pathophysiology of the disease. The aim of this study was to analyze the hemorheological profile after stripping in 45 patients suffering from CVI. Follow-up included laboratory tests on the 7th, 60th and 180th day after surgery. EA was assessed with a photometric aggregometer (MA1, Myrenne) in stasis and low shear (3 s(-1)). The results show an increase of EA on the 7th day after surgery (p<0.001). Two and 6 months later, EA values returned to those found prior to surgery. The plasma fibrinogen level changes in a way parallel to EA. The association between rheological disturbances and thrombogenesis is well known, so the hyperaggregability found supports the antithrombotic prophylaxis in the early postsurgical period. On the other hand, the hemorheological abnormalities persist after stripping, so postsurgical treatment to inhibit EA may be beneficial.

Adult↗

A phase II study of gemcitabine in platinum pre-treated patients with advanced epithelial ovarian cancer.

BACKGROUND: Most patients with advanced ovarian cancer will relapse following platinum-based combination chemotherapy and be considered for second-line treatment. Gemcitabine, a nucleoside analogue, is active against a range of solid tumors. This phase II study investigated the activity of single-agent gemcitabine in patients with recurrent ovarian cancer. PATIENTS AND METHODS: Thirty-eight patients with FIGO stage III (34%) or IV (64%) ovarian cancer who were previously treated with platinum-containing regimens were enrolled. Patients received 1200 mg/m2 gemcitabine on days 1, 8 and 15 of a 28-day cycle. RESULTS: Patients completed an average of 3.6 cycles. Two complete and three partial responses were seen in 36 evaluable patients, for an overall response rate of 13.9% (95% CI: 4.7%-29.5%). The median survival time was 6.7 months. Toxicities were generally mild. The most common were grade 3-4 neutropenia and grade 3 leukopenia reported in 23.7% and 10.5% of patients, respectively. One patient had grade 4 pulmonary toxicity. CONCLUSION: Single-agent gemcitabine is active and well tolerated in patients with recurrent ovarian cancer.

Adult↗

Eradication and follow-up of Helicobacter pylori infection in hemodialysis patients.

It is currently accepted that Helicobacter pylori (Hp) infection is crucial in the pathogenesis of peptic ulcer. Therefore, we developed a prospective study to assess the prevalence of Hp infection by the 13C Urea Breath Test (13C UBT) in 52 hemodialysis patients, and we evaluated the efficacy of two consecutive eradication regimens in 23 positive patients with dyspepsia and/or on a transplantation list. The correlation between anti-Hp serology and 13C UBT results was also analyzed in 34 patients who were followed up during 18 months. The Hp prevalence by 13C UBT was 63.5% (33/52). The eradication rate after the first cycle of therapy (amoxicillin 500 mg/8 h and omeprazole 20 mg/12 h, 14 days) was 60.8% (14/23). After the second cycle (clarithromycin 500 mg/12 h plus omeprazole 20 mg/12 h, 14 days), the eradication rate reached 82.6% (19/23). The serological procedure showed a good correlation with 13C UBT (about 80% sensitive and specific) when very restrictive diagnostic and eradication criteria were adopted. We conclude that an eradication rate higher than 80% can be reached after two consecutive cycles of dual therapy in hemodialysis patients. Anti-Hp serological tests must be cautiously interpreted in these patients.

Aged↗

[Hypercoagulability status previous to total hip and knee arthroplasty: the contribution of rheumatoid arthritis].

PURPOSE: Starting from a status hypercoagulability previous to substitutive hip and knee surgery, the aim of this work was to investigate the influence of different osteoarthropatic pictures for which arthroplasty is indicated in the activation of the clotting cascade, rheumatoid arthritis (RA) being one of such pictures. PATIENTS AND METHODS: Of 79 patients suitable for prosthetic surgery of hip (53) and knee (26), the preoperative values of several markers, namely, D dimers (D-D), thrombin-antithrombin (TAT) complex, and F1 + 2 prothrombin fragment (F1 + F2) were assessed by enzymoimmunoasay. The mean age of the patients was 65.5 years, and their sex distribution was 50 women and 29 men. The indications for arthroplasty were as follows: osteoarthrosis (62), aseptic necrosis (11), RA (9), articular gout (2), previous fracture (2), more than one diagnosis overlapped in some cases. The results attained were compared with a control group comprised of 33 subjects (16 women and 17 men) with mean age similar to the patient's group (68.06 years). RESULTS: The D-D values in the patients suitable for hip arthroplasty and the TAT values in patients suitable for both types of surgery were significantly higher than those found in the control group (p = 0.012 and 0.01, respectively). The preoperative TAT levels of the RA patients were significantly higher (p = 0.025) than those found in the patients with the other surgical indications. CONCLUSIONS: Previously to the performance of arthroplasty, the patients show hypercoagulative marker values higher than those of age-matched controls. The significant rising of TAT found in RA patients is concordant with the literature, and this fact makes it advisable to include RA among the pathologic situations associated with hypercoagulability, as this is a common indication for substitutive hip and knee surgery with high risk of venous thromboembolic disease.

Aged↗

Activation of arylamines to mutagenic product(s) by two in vitro plant systems.

Plant activation of three isomers of phenylenediamine o- m- and p-phenylenediamine, has been studied. Two in vitro plant systems have been used: Persea americana S117 with mixed-function oxidase (MFO) and peroxidase activities, and Zea mays S9 which contains only peroxidase activity. As genetic endpoint, the classical Salmonella tester strains. TA98 and TA100, their derivatives with high O-acetyltransferase levels (YG1024 and YG1029, respectively) and TA98/1.8-DNP6, deficient in this enzyme, have been assayed. Of the three isomers studied, only m-PDA was activated to mutagenic product(s) by both plant systems. This activation required the bacterial O-acetyltransferase activity to give frameshift mutagenic product(s), detected in TA98 and YG1024 strains. In all the assays the P americana system was more potent than the Z. mays system in activating m-PDA. A slight increase of the number of YG1029 revertants was detected when m-PDA was activated by P. americana, suggesting that this compound can be also converted into ultimate mutagenic product(s) that induce base-pair substitutions. m-PDA activation by Z. mays was dependent on the peroxidase activity of this system, but the activation produced by P. americana was totally dependent on MFOs, because a total inhibition of the mutagenic response was found when these activities were inhibited. In addition, the P. americana system was more potent in generating proximal mutagenic forms from m-PDA than S9 from non-induced rat liver, although S9 from Aroclor 1254-induced Sprague-Dawley male rats was the most potent system in the m-PDA activation. These results indicate that the P. americana system can be useful in determining the role of mixed-function oxidases in plant activation of xenobiotics.

Animals↗

Prevalence and seasonal activity of Ixodes ricinus (Acari:Ixodidae) on domestic ruminants of the Basque country, Spain.

Ixodes ricinus on domestic ruminants was sampled through a natural year at several points in the Basque country, north Spain. The sampling points were comprised of the different natural regions, according to climate and vegetation, into which the region is commonly divided. Both the immature and adult stages were collected on cattle and sheep at five of the eight collecting points, namely in areas with a medium elevation, mild summers and a medium to high annual rainfall. The adults of this tick showed a bimodal pattern of activity in some areas, while in others the pattern was unimodal. It was concluded that, because of the adequate climate, I. ricinus is widely distributed in the Basque country, with geographically close populations adapted to different, local, changing conditions.

Animals↗

UFT in combination as adjuvant therapy for breast cancer. Grupo Oncologico de Sevilla Seville, Spain.

Between 1989 and 1993, 409 evaluable patients with breast cancer have been treated with tegafur and uracil (UFT) in an adjuvant setting in two different trials. Data from both trials were reviewed in December 1995 after a mean follow-up of 5.09 +/- 1.1 years (range, 2.9 to 7.1 years). The aim of the first trial was to demonstrate the activity of UFT 400 mg/day for 6 months plus prednimustine 60 mg/m2 for 7 consecutive days, every 28 days in 6 cycles given orally (arm B). This scheme was compared with 6 cycles of cyclophosphamide 600 mg/m2, plus methotrexate 40 mg/m2, plus fluorouracil 600 mg/m2, every 4 weeks (arm A). In this study, 187 premenopausal women were evaluable, 96 in arm A and 91 in arm B, all of whom had positive axillary nodes. Although there were more younger patients in arm A than in arm B, prognostic factors were similar in both groups. Disease-free survival and overall survival were similar in both arms. However, some concern is raised by the low disease-free survival rate. The toxicity was mild (mainly nausea and vomiting and alopecia) and slightly worse in arm A. We believe that oral administration could be a useful alternative to the parenteral route. In the second trial, 222 evaluable patients received 20 mg/day of tamoxifen (Nolvadex) for 1 year (arm A), or the same dose of tamoxifen plus UFT 400 mg/day for 6 months. All patients were postmenopausal, and the characteristics of the tumors were the same as those in patients in the first trial. In arm A there were 109 patients and in arm B, 113. The groups were well balanced. The overall survival and the disease-free survival rates were equal in both arms, but were longer in arm B in the subset of patients with five or more axillary-involved nodes. The toxicity was negligible in both arms. We conclude that UFT/tamoxifen might be useful in postmenopausal patients with five or more involved nodes who are unable to follow a more aggressive schedule because of their age or low performance status.

Administration, Oral↗

[Comparative study of 2 antithrombotic regimens in 75 patients with coronary endoprostheses].

PURPOSE: To compare systemic anticoagulation with antiaggregation in patients with coronary stent, with regard to subacute occlusion, mean hospital staying and haemorrhagic complications. PATIENTS AND METHODS: Seventy-five patients with coronary stent were treated with one of two different antithrombotic protocols. A group comprised of 34 patients (group A) received sodium heparin and acenocoumarin, plus acetylsalicylic acid (325 mg) and dipyridamole (225 mg). The remaining 41 patients (group B) were given antiplatelet agents, namely ticlopidine (125-250 mg) and aspirin (125 mg). RESULTS: One case of group A (2.9%) showed thrombosis due to stent occlusion. No thrombotic complications were seen in the patients with antiplatelet drugs. Haemorrhagic complications were present in 11 group A patients (32.3%), and blood transfusion was necessary in 3 of them. Hemorrhage was present in 9 cases of group B (21.8%), and none of them needed blood transfusion. The mean number of days to achieve INR > 2 was 3.06 (1-11) in group and 2.02 (1-5) in group B. CONCLUSIONS: Antiplatelet regimes appear as a good choice in coronary stent, in spite of the fact that the primary indication seems that of group A.

Acenocoumarol↗

Inhibition of D-amino acid oxidase by alpha-keto acids analogs of amino acids.

The inhibition of D-amino acid oxidase by certain alpha-keto acids products of the reaction with D-amino acids, in particular alpha-keto acids that are analogs of the amino acids alanine, valine, leucine, phenylanaline, phenylglycine, tyrosine and tryptophan, is reported. All the alpha-keto acids assayed behaved as substrate competitive inhibitors of the enzyme. The relationship between the degree of inhibition and the structure of the inhibitor is discussed.

Amino Acids↗