Biomedical subjects

M Viana

Publications and source records attributed to M Viana.

At least 19 recordsLinked to original sources

PubMed2003

Cancer risk around the nuclear power plants of Trillo and Zorita (Spain).

AIM: To investigate the association between cancer risk and proximity of place of residence to the Guadalajara nuclear power plants: Trillo and Zorita. METHODS: Case-control study. Cases were patients admitted with cancer and controls were non-tumorous patients, both admitted to Guadalajara Hospital (period 1988-99). Exposure factor: place of residence (areas within 10, 20, and 30 km of each plant). Odds ratios (ORs) of those areas closest to the plants were calculated with respect to those furthest away; a linear trend analysis was also performed. RESULTS: In the extreme areas in the vicinity of Trillo, an OR of 1.71 was obtained (95% CI 1.15 to 2.53), increasing in magnitude in the subgroup of more radioinducible tumours and in the period considered as post-latency (1997-99). Risk increased linearly with proximity to the two plants, significantly in Trillo (p < 0.01) but not in Zorita (p = 0.19). CONCLUSIONS: There is an association between proximity of residence to Trillo and cancer risk, although the limitations of the study should be kept in mind when interpreting the possible causal relation.

Adult↗

PubMed2002

Effects of ergothioneine on diabetic embryopathy in pregnant rats.

The natural antioxidant ergothioneine (2-mercaptohistidine trimethylbetaine) is a fungal metabolite and found in most plant and animal tissues. The effect of ergothioneine on diabetic embryopathy in rats was assessed. Supplementation of diabetic pregnant rats with L-ergothioneine (1.147 mg/kg body weight) daily for the first 11.5 days of pregnancy reduced the rate of embryo malformations, to values similar to the non-diabetic animals. The ergothioneine had no effect on the plasma glucose levels, both in diabetic and control animals. We conclude that the inhibition of the glucose-mediated free radical dependent embryo malformation by ergothioneine is an important antioxidant prophylactic mechanism, which when combined with vitamin E could benefit the management of diabetic embryopathy.

Animals↗

PubMed2002

Influence of manufacturing process on tabletting ability of powder: comparison between blending, grinding, and spray drying of two formulations made of theophylline and lactose/cellulose or Cellactose.

Three manufacturing processes were applied to two formulations composed of 20% anhydrous theophylline associated with either 20% microcrystalline cellulose and 60% lactose or 80% Cellactose. The processing method (dry blending, grinding, or spray drying) and the formulation were investigated through the comparison of the physical and flow characteristics and the compactibility of the end products. The results demonstrated that the formulation had a major effect on the mechanical properties, with binary blends exhibiting a higher resistance than ternary ones, whereas flow properties and densification depended on the process. Nevertheless, it was also observed that spray drying decreased the difference between the mechanical properties of the two formulations, probably by modifying the texture of the Cellactose in suspension.

Bronchodilator Agents↗

PubMed2001

Pilot trial of interleukin-2 with granulocyte colony-stimulating factor for the mobilization of progenitor cells in advanced breast cancer patients undergoing high-dose chemotherapy: expansion of immune effectors within the stem-cell graft and post-stem-cell infusion.

PURPOSE: To evaluate whether administration of interleukin-2 (IL-2) with granulocyte colony-stimulating factor (G-CSF) improves mobilization of immune effector cells into the stem-cell graft of patients undergoing high-dose chemotherapy and autografting. PATIENTS AND METHODS: We performed a trial of stem-cell mobilization with IL-2 and G-CSF in advanced breast cancer patients receiving high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin and stem cells followed by IL-2. The trial defined immune, hematologic, and clinical effects of IL-2 in this setting. RESULTS: Of 32 patients enrolled, nine received G-CSF alone for mobilization. Twenty-one of 23 patients mobilized with IL-2 plus G-CSF had stem cells collected with more mononuclear cells than those receiving G-CSF (19.3 v 10.4 x 10(8)/kg; P =.006), but fewer CD34(+) progenitor cells (6.9 v 22.0 x 10(6)/kg; P =.049). The IL-2 plus G-CSF-mobilized patients had greater numbers of activated T (CD3(+)/CD25(+)) cells (P =.009), natural killer (NK; CD56(+)) cells (P =.007), and activated NK (CD56 bright(+)) cells (P: =.039) than those patients mobilized with G-CSF. NK (P =.042) and lymphokine-activated killer (LAK) (P =.016) activity was increased in those mobilized with IL-2 + G-CSF, whereas G-CSF-mobilized patients had a decline in cytolytic activity. In the third week posttransplantation, immune reconstitution was superior in those mobilized with IL-2 plus G-CSF based on greater numbers of activated T cells (P =.003), activated NK cells (P =.04), and greater LAK activity (P =.003). The 16 of 21 IL-2 + G-CSF-mobilized patients with adequate numbers of stem cells (> 1.5 x 10(6) CD34(+) cells/kg) collected engrafted rapidly posttransplantation. CONCLUSION: The results demonstrate that G-CSF + IL-2 can enhance the number and function of antitumor effector cells in a mobilized autograft without impairing the hematologic engraftment, provided that CD34 cell counts are more than 1.5 x 10(6) cells/kg. Mobilization of CD34(+) stem cells does seem to be adversely affected. In those mobilized with IL-2 and G-CSF, post-stem-cell immune reconstitution of antitumor immune effector cells was enhanced.

Adult↗

PubMed2001

About the use of stoichiometric hydroxyapatite in compression - incidence of manufacturing process on compressibility.

Literature concerning calcium phosphates in pharmacy exhibits the chemical diversity of the compounds available. Some excipient manufacturers offer hydroxyapatite as a direct compression excipient, but the chemical analysis of this compound usually shows a variability of the composition: the so-called materials can be hydroxyapatite or other calcium phosphates, uncalcined (i.e. with a low crystallinity) or calcined and well-crystallized hydroxyapatite. This study points out the incidence of the crystallinity of one compound (i.e. hydroxyapatite) on the mechanical properties. Stoichiometric hydroxyapatite is synthesized and compounds differing in their crystallinity, manufacturing process and particle size are manufactured. X-Ray diffraction analysis is used to investigate the chemical nature of the compounds. The mechanical study (study of the compression, diametral compressive strength, Heckel plots) highlights the negative effect of calcination on the mechanical properties. Porosity and specific surface area measurements show the effect of calcination on compaction. Uncalcined materials show bulk and mechanical properties in accordance with their use as direct compression excipients.

Calcium↗

PubMed2001

Comparative study of PCR as a direct assay and ELISA and AGID as indirect assays for the detection of bovine leukaemia virus.

The choice of a diagnostic method depends on the characteristics of the herd to be analysed. Two herds with different prevalences of enzootic bovine leukaemia were chosen to study the concordance between agar gel immunodiffusion (AGID), enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) methods. PCR, an increasingly used virological method, was performed with four sets of primers, amplifying different genomic regions (env, pol and tax), from DNA extracted either from peripheral blood monocytes (PBMCs) or milk leucocytes. The highest percentage of positive animals was obtained using PCR performed with DNA extracted from PBMCs using primers which amplified either env or pol, followed by PCR using PBMCs and primers which hybridized with tax, then ELISA using serum and finally AGID. The results of PCR were more consistent with PBMCs than when milk leucocytes were used.

Animals↗

PubMed2000

Oxidative damage in pregnant diabetic rats and their embryos.

Free radical mechanisms may be involved in the teratogenesis of diabetes. The contribution of oxidative stress in diabetic complications was investigated from the standpoint of oxidative damage to DNA, lipids, and proteins in the livers and embryos of pregnant diabetic rats. Diabetes was induced prior to pregnancy by the administration of streptozotocin (45 mg/kg). Two groups of diabetic rats were studied, one without any supplementation (D) and another treated during pregnancy with vitamin E (150 mg/d by gavage) (D + E). A control group was also included (C). The percentage of malformations in D rats were 44%, higher than the values observed in C (7%) and D + E (12%) animals. D Group rats showed a higher concentration of thiobarbituric acid reactive substances in the mother's liver, however, treatment with vitamin E decreased this by 58%. The levels of protein carbonyls in the liver of C, D, and D + E groups were similar. The "total levels" of the DNA adducts measured, both in liver and embryos C groups were similar to the D groups. Treatment of D groups with vitamin E reduced the levels by 17% in the liver and by 25% in the embryos. In terms of the "total levels" of DNA adducts, the embryos in diabetic pregnancy appear to be under less oxidative stress when compared with the livers of their mothers. Graziewicz et al. (Free Radical Biology & Medicine, 28:75-83, 1999) suggested "that Fapyadenine is a toxic lesion that moderately arrests DNA synthesis depending on the neighboring nucleotide sequence and interactions with the active site of DNA polymerase." Thus the increased levels of Fapyadenine in the diabetic livers and embryos may similarly arrest DNA polymerase, and in the case of this occurring in the embryos, contribute to the congenital malformations. It is now critical to probe the molecular mechanisms of the oxidative stress-associated development of diabetic congenital malformations.

Adenine↗

PubMed2000

Interleukin 10-induced thrombocytopenia in normal healthy adult volunteers: evidence for decreased platelet production.

Recombinant human interleukin 10 (rhuIL-10) inhibits the production of proinflammatory cytokines and has shown promise in the treatment of inflammatory bowel disease. Clinical trials have been accompanied by a reversible decline in platelet counts. We conducted a randomized, double-blinded, placebo-controlled, parallel group trial in 12 healthy volunteers to investigate the aetiology of rhuIL-10-induced thrombocytopenia. Eight volunteers received 8 microg/kg/d of rhuIL-10 subcutaneously, while four subjects received a placebo alone for 10 d. A reversible decline in the platelet counts from a mean of 275 x 10(9)/l to 164 x 10(9)/l was observed in the IL-10-treated cohort (P = 0.012). A fall in the haemoglobin mean levels was also observed in the IL-10-treated cohort from 13.7 to 11.7 g/dl (P = 0.011). No significant change was observed in the bone marrow cellularity or myeloid/erythroid ratio or in the number of megakaryocytes per high-powered field (HPF). A fall was observed in the number of megakaryocyte colony-forming units (CFU-MKs) after the administration of IL-10 compared with those receiving the placebo (P = 0.068). No difference in the change in granulocyte-macrophage CFUs (CFU-GMs), mixed lineage CFUs (CFU-GEMMs) or erythroid burst-forming units (BFU-Es) was observed when comparing the IL-10- vs. placebo-treated groups (P > 0.465). Serum cytokine levels of thrombopoietin (TPO). IL-6 and granulocyte-macrophage colony stimulating factor (GM-CSF) were not decreased following IL-10 administration. In fact, both TPO and GM-CSF appeared to be slightly increased in the serum. All subjects underwent In111-labelled platelet survival studies with liver/spleen scans to assess splenic sequestration prior to and then on day 7 of treatment. A significant reduction in splenic sequestration of platelets (P =0.012) was observed in the IL-10-treated group, but not in the placebo-treated subjects.

Adult↗

PubMed2000

Symmetrically dependent models arising in visual assessment data.

Given data from bilateral visual assessments on N subjects at k occasions, we consider inference for contralateral correlations (C) between fellow eyes and lateral correlations (L) among p different assessments of the same eye. Under permutation symmetric dependence structure between observations from fellow eyes and among observations from the same eye, we obtain maximum likelihood estimates of L, C, and L-C. Based on the large-sample estimates of the corresponding covariance structures, we test the hypothesis that the association between fellow eyes is constant across time and the hypothesis that lateral and contralateral associations between any two occasions are the same.

Biometry↗

PubMed1999

Comparison of sotalol versus quinidine for maintenance of normal sinus rhythm in patients with chronic atrial fibrillation.

Many clinicians choose sotalol for the prevention of recurrences of atrial fibrillation (AF) as an alternative to quinidine, which has been associated with an increase in long-term mortality. Using meta-analytic techniques, we compared the effects on maintenance of sinus rhythm and mortality of combined groups of patients with chronic AF treated with sotalol, quinidine, or a control drug. Rates of conversion at 6 months and mortality were combined for each group after performing sensitivity analysis to test for homogeneity. Bayesian estimates and corresponding 95% credibility intervals were constructed to compare the probabilities of achieving sinus rhythm and mortality among groups. A literature search revealed 4 sotalol studies, 6 quinidine studies, and 5 control studies that met inclusion criteria established a priori. The point estimates for maintaining normal sinus rhythm (at 6 months) and corresponding credibility intervals for the 3 groups were sotalol 50% (range 42% to 58%), quinidine 53% (range 48% to 59%), and control 32% (range 26% to 39%). When combining and comparing mortality effects, the following studies met the same inclusion criteria: 4 sotalol studies, 9 quinidine studies, and 7 control studies. The point estimates and corresponding credibility intervals for mortality in the 3 groups were sotalol 2.2% (range 0.6% to 4.8%), quinidine 3.0% (range 1.7% to 4.7%), and control 1.1% (range 0.3% to 2.4%). Sotalol and quinidine are comparable in their ability to maintain sinus rhythm at 6 months (about 50%) and both agents are superior to control. There is a trend for both agents to increase mortality with long-term therapy. These data do not support choosing sotalol over quinidine as a safer alternative for preventing recurrences of chronic AF.

Anti-Arrhythmia Agents↗

PubMed1999

Cost considerations of medical therapy for glaucoma.

PURPOSE: To determine the calculated daily patient cost (cost minimization) of medical glaucoma therapy. METHODS: The actual volume of various glaucoma medications was determined for all commercially available sizes of the tested products. The drops per ml on the basis of the actual volume and the daily costs of the dosage schedules recommended by the manufacturers were compared. The cost of each bottle of medication was determined from the average wholesale price in the United States. RESULTS: The generic timolol products dosed twice daily and the once-daily gel-forming solutions (range, $0.30 to $0.46/day) were similar on a cost-per-day basis compared with the brand name metipranolol (Optipranolol; Bausch & Lomb Pharmaceuticals, Tampa, Florida, at $0.43/day) and timolol (Timoptic; Merck, West Point, Pennsylvania, at $0.46/day and Timoptic XE at $0.38/ day). Betaxolol (Betoptic S; Alcon Laboratories, Fort Worth, Texas, at $0.65/day), carteolol (Ocupress; CibaVision, Duluth, Georgia, at $0.57/day), levobunolol ($0.61/day), and brand name levobunolol (Betagan; Allergan, Irvine, California, at $0.81/day) all were dosed twice daily and were more costly on a per-day basis. The topical carbonic anhydrase inhibitors brinzolamide (Azopt; Alcon, at $0.96/day) and dorzolamide (Trusopt; Merck, at $1.02/day) were dosed three times daily and were similar on a cost-per-day basis. The combination product Cosopt (timolol 0.5% + dorzolamide 2.0%, Merck, at $1.12/day) was less costly than separate bottles of a topical carbonic anhydrase inhibitor (three times daily dosing) and a beta-blocker ($1.26 to $1.83/day), often even if the topical carbonic anhydrase inhibitor was dosed two times daily ($0.94 to $1.49). The selective alpha2-agonist brimonidine (Alphagan; Allergan, at $0.90/day) twice daily and the prostaglandin analog latanoprost (Xalatan; Pharmacia & Upjohn, Kalamazoo, Michigan, at $0.92/day) once daily were similarly priced. CONCLUSIONS: All generic timolol, Optipranolol, Timoptic, and Timoptic XE ranged between $0.30 and $0.46 per day. Betaxolol, Ocupress, generic levobunolol, and Betagan were more costly, ranging between $0.57 and $0.81 per day. Cosopt ($1.12/day) was less costly than separate bottles of a topical beta-blocker and a topical carbonic anhydrase inhibitor dosed three times daily ($1.26 to $1.83/day) and often twice daily ($0.94 to $1.49). Alphagan and Xalatan were similarly priced ($0.90/day and $0.92/day, respectively). This study is based on a best-case scenario for all medicines and does not account for wasted doses, the frequency of refills, or a medication's success or failure rate. New adjunctive glaucoma regimens exhibit similar costs per day compared with more traditional regimens.

Adrenergic alpha-Agonists↗

PubMed1999

Alpha-tocopherol concentration in fetal and maternal tissues of pregnant rats supplemented with alpha-tocopherol.

We wanted to determine whether alpha-tocopherol supplementation to pregnant rats could increase the concentration of alpha-tocopherol in maternal and fetal plasma and tissues. Pregnant rats were treated with alpha-tocopherol on days 18 and 19 gestation and studied at day 20. A control group was studied in parallel. Treatment of pregnant rats with alpha-tocopherol increased its concentration in maternal and fetal plasma, in all maternal plasma lipoprotein fractions, in maternal and fetal liver and in the placenta. The fetal and maternal concentration of alpha-tocopherol were positively correlated.

Animals↗

PubMed1997

Simultaneous determination of vitamins A and E in rat tissues by high-performance liquid chromatography.

A high-performance liquid chromatographic (HPLC) method to determine vitamins A, Ap and E simultaneously was developed with direct extraction of vitamins from rat tissues with n-hexane and probe sonicating. The dry residue was redissolved in chloroform-methanol. Vitamins A and Ap were detected by UV-Vis and vitamin E by fluorescence. Vitamin K, used as internal standard, was detected both the UV-Vis and by fluorescence. Standards and samples were checked for linearity giving correlation coefficients that were higher than 0.99 in the concentration range of 3.1-9.4 for vitamin A, 8.2-24.7 for vitamin Ap and 0.6-1.7 nmol/g in the case of liver extracts and 0.5-3.0 nmol/g in the case of placenta. The inta-assay precision (R.S.D) varied between 1.48 and 7.25, whereas inter-assay precision was between 4.99 and 7.03. Recoveries ranged between 94 +/- 8 and 107 +/- 5%. Results from the application of this method to different rat tissues having wide range of vitamin content are presented.

Animals↗

PubMed1997

Antioxidant and prooxidant effects of ascorbic acid, dehydroascorbic acid and flavonoids on LDL submitted to different degrees of oxidation.

UNLABELLED: Although a high intake of antioxidants may decrease the risk of developing cardiovascular diseases, under certain circumstances they may promote free radical generation and lipid peroxidation. The objectives of the present study were to determine the antioxidant effects of ascorbic acid (AA), dehydroascorbic acid (DHA) and flavonoids on LDL submitted to different degrees of oxidation. LDL was submitted to oxidation with CuCl2 (2.4 microM). Before or at different times after the propagation of the oxidation process, 28 microM (5 micrograms/ml) of either AA or DHA or 5 micrograms/mL flavonoids extract were added. Alpha-tocopherol, conjugated dienes, thiobarbituric acid reacting substances (TBARS) and LDL electrophoretic mobility were determined as indices of LDL oxidation. The presence of any of the three antioxidants from the onset of the incubation delayed the oxidation process. However, the addition of both DHA and flavonoids to the oxidation process when it was already initiated and alpha-tocopherol consumed, accelerated the oxidation. In contrast, AA delayed the oxidation process even when added after alpha-tocopherol was consumed. Nevertheless, it also accelerated LDL oxidation when added during the propagation phase of the oxidation process. IN CONCLUSION: although AA, DHA and flavonoids delay LDL oxidation when added before the initiation of the process, they accelerate the process if added to minimally oxidized LDL.

Adult↗

PubMed1997

Polyhexamethylene biguanide (PHMB) in the treatment of experimental Fusarium keratomycosis.

PURPOSE: We wanted to determine whether topical polyhexamethylene biguanide (PHMB) 0.02% was effective in the treatment of experimental Fusarium keratomycosis in rabbits. METHODS: Fusarium solani keratomycosis was induced in the eyes of 12 New Zealand white rabbits. The rabbits were treated with PHMB 0.02% in one eye and placebo in the other eye for 6 days. The rabbits were evaluated in a masked fashion using a standardized system for clinical progression of the disease. Then the corneas were trephined and growth of F. solani in colony-forming units per milliliter (CFU/ml) determined. RESULTS: Clinical evaluation demonstrated no significant mean difference (p > 0.10) in clinical scores between treated and control eyes on day 6 (0.583 +/- 2.503). There was a significant mean CFU difference (p = 0.06) between treated eyes and control eyes (182.5 +/- 314.44). Seven of 12 eyes (58%) in the PHMB group exhibited no growth, whereas two of 12 (17%) eyes reported no growth in the control group. One of 12 eyes (8%) reported > 100 CFU in the PHMB group, whereas seven of 12 eyes (58%) reported > 100 CFU in the control group. CONCLUSIONS: PHMB 0.02% was effective in significantly reducing the fungal growth in our rabbit model of Fusarium keratomycosis. The future role of PHMB in the treatment of Fusarium keratitis needs to be further evaluated.

Administration, Topical↗

PubMed1996

Teratogenic effects of diabetes mellitus in the rat. Prevention by vitamin E.

We wanted to determine whether administration of vitamin E could reduce the production of free radicals which could play a role in the teratogenic effects of diabetes mellitus. Diabetes was induced in Wistar rats by the intravenous administration of streptozotocin. The animals were divided into six groups: one with no supplement (D) and two, supplemented during pregnancy either with oral vitamin E (150 mg/day) (D + E) or with a placebo (safflower oil) (D + O). Three other groups were kept under the same conditions, but were treated with insulin: D + I, D + I + E and D + I + O. There were three groups of matched controls: C, C + E and C + O. All animals were killed on day 11.5 of pregnancy. In C animals the percentages of reabsorptions and malformations were 1.3 and 2%, respectively, compared with 23.6, 24.3, 6.2 and 13.2%, respectively in D and D + I groups. The crown-rump length, number of somites, and protein and DNA content were higher in C animals than in the diabetic rats, independent of insulin treatment. When vitamin E was administered no changes in these parameters were observed in C and D + I animals; however, in the D mothers it reduced the rate of embryo malformations to 4.6% and increased the crown-rump length and the number of somites. However, vitamin E did not modify the protein and DNA content and the percentage of reabsorptions. In conclusion, administration of vitamin E to diabetic animals decreases the rate of embryo malformations and increases their size and maturation, supporting a role for free radicals in the teratogenic effects of diabetes.

3-Hydroxybutyric Acid↗

PubMed1996

In vitro effects of a flavonoid-rich extract on LDL oxidation.

Flavonoids are phenolic compounds of vegetable origin with antioxidant effects. The present study aimed to determine their properties as LDL antioxidants. LDL were incubated with increasing concentrations of flavonoids (0-16 micrograms/ml) and LDL oxidation was started by adding CuCl2 (2 microM) to the media. When flavonoids were present in the media, vitamin E consumption, the lag phase of conjugated diene formation, LDL electrophoretic mobility in agarose gels and the appearance of thiobarbituric acid reacting substances (TBARS) were delayed in a concentration-dependent manner. To determine whether flavonoids could terminate LDL oxidation once initiated, two sets of experiments were performed. In the first, LDL oxidation was initiated as described above. At 2 or 4 h of incubation, flavonoids were added (4 micrograms/ml) and their effect compared to samples where butylated hydroxytoluene or EDTA were added. At 5 h, in the LDL samples where flavonoids were added, the electrophoretic mobility and TBARS production were the same as those present in LDL samples incubated for the whole period in the absence of flavonoids. However, when either butylate hydroxytoluene or EDTA was added, as would be expected, the LDL oxidation process was completely arrested as shown by a reduction in the appearance of TBARS and a lower LDL electrophoretic mobility. In the second experiment, LDL oxidation was initiated as described above and at 0, 10 and 20 min, flavonoids were added (4 micrograms/ml). When vitamin E was still present in the LDL solution, the flavonoids were able to both increase the lag phase in the formation of conjugated dienes and to delay the consumption of vitamin E. The present results show that in vitro, flavonoids prevent LDL oxidation in a concentration-dependent manner, delaying the consumption of vitamin E, but they cannot terminate or delay LDL oxidation once vitamin E in LDL is consumed.

Antioxidants↗

PubMed1995

Relative effects of age and compromised vision on driving performance.

The aim of this study was to determine the relative effects of age and compromised vision on driving-related skills and on-road accidents. A total of 107 subjects were tested. They represented four groups that varied in age and visual status, as follows: (1) a younger, normally sighted group; (2) an older, normally sighted group; (3) a younger, visually compromised group; and (4) an older, visually compromised group. Driving performance was assessed by self-reported and state-recorded accident frequency and by an evaluation of performance on an interactive driving simulator. The older groups had poorer driving-related skills, as measured with our interactive driving simulator, than had the younger groups, but they did not have significantly higher on-road accident rates than the younger groups. The older subjects and those with compromised vision had reduced risk-taking scores, as measured with a self-report questionnaire. In addition, all older drivers had increased eye movements and had slower simulator driving speeds, which suggests that behavioral compensation is made for visuocognitive/motor deficits. Regression analyses showed that compromised vision and visual field loss predicted real-world accidents in our study population.

Accidents, Traffic↗