Oil oxidation in corn flour from grains processed with alkaline cooking by use of peroxide value, UV and FTIR.

The objective of this work was to evaluate the effect of alkaline cooking on the oxidative stability of oil in corn flour. A central composite design was used to study the combined effect of lime concentration (%) and steep time (h) on peroxide value (PV); specific extinction coefficients at 232 and 270 nm (K232 and K270); and FTIR absorbance at 3009 cm(-1), 3444 cm(-1), and 3530 cm(-1) in oils from corn flour obtained by alkaline cooking. The results indicate that lime concentration and steep time affected the PV, K232, and K270. A decrease of 2.56 % was observed in the IR absorption bands, corresponding to the polyunsaturated fatty acids. The FTIR spectra also showed absorption bands related to the secondary oil oxidation products.

Red fluorescent benzothiadiazole derivative loaded in different nanoformulations: Optical properties and their use in bio-imaging.

Fluorophores with optimized nonlinear optical properties have become prominent as contrast labels in laser scanning microscopy (LSM). The purpose of this work is to report on a novel benzothiadiazole derivative, namely 4,7-bis(5-((9,9-dioctyl-9H-fluoren-2-yl)ethynyl)thiophen-2-yl)benzo[c][1,2,5]thiadiazole (EFBT) and its optical performance when it is loaded into organic nanostructures intended as labels for LSM. Four different nanostructured labels were prepared: i) EFBT-loaded silica nanoparticles (SiNPs); ii) folate-bioconjugated SiNPs (SiNPs-FA); iii) EFBT-loaded PEGylated nanoparticles (NPs-PEG); and iv) EFBT-loaded folate-terminated PEGylated nanoparticles (NPs-PEG-FA). All these nanostructures are reported through a comparative study of their linear and nonlinear optical properties, including their performance as exogenous label agents in the cervical cancer cell line HeLa. This assessment of the performance of a specific fluorophore loaded into different nanostructured matrices (labels), and fairly compared under the same characterization conditions, including the LSM settings, is less common while previous reports had focused in comparing silica and PEGylated nanoparticles but loaded with different fluorophores. The results show that the internal molecular organization into each type of organic nanostructure impacted differently the properties of EFBT, where the silica matrix tend to preserve the optical performance of the fluorophore by preventing intermolecular interactions; in contrast, PEGylated nanoparticles favored molecular interactions and introduced non-radiative decay channels that degrades drastically the optical performance. Nevertheless, the use of functionalized ends entities produced a better cellular label uptake with PEGylated that with silica nanoparticles. In overall, the NPs-PEG-FA label produced the best HeLa imaging.

Enhancement of opiate analgesia by nimodipine in cancer patients chronically treated with morphine: a preliminary report.

The ability of nimodipine, a calcium-channel blocker, to enhance morphine analgesia and/or modify the development of tolerance was studied in patients with cancer pain who had needed successive increments of morphine for periods ranging from 21 to 780 days. Assessment of daily morphine consumption was the primary effect parameter. Nimodipine succeeded in reducing the daily dose of morphine in 16 of 23 patients (oral, n = 13; intrathecal, n = 3), and failed to modify it in 2 patients. Total oral daily dose was reduced by nimodipine (120 mg/day) from 282.6 +/- 47.7 mg to 158.7 +/- 26.2 mg (n = 15, P < 0.001). Intrathecal morphine was also reduced by 1-5 mg/day. Nimodipine was withdrawn in 5 patients during the first week of treatment due to intolerance (n = 3) or aggravation of the disease (n = 2). These preliminary results support experimental findings showing that pharmacological interference with Ca(2+)-related events may modify chronic opioid effects, including the expression of tolerance.

Nimodipine-enhanced opiate analgesia in cancer patients requiring morphine dose escalation: a double-blind, placebo-controlled study.

The ability of nimodipine, a dihydropyridine calcium antagonist, to reduce the daily dose of oral morphine in cancer patients who had developed dose escalation, was tested in 54 patients under randomized, double-blind, placebo-controlled conditions. We selected patients that required at least two successive increments of morphine to maintain pain relief. A possible pharmacokinetic interaction between nimodipine and morphine was also studied in 14 patients by assaying steady-state serum levels of morphine and its 3- and 6-glucuronides. A total of 30 patients completed the study, 14 and 16 in the nimodipine and placebo groups, respectively. Nimodipine controlled the escalation of the morphine dose in 9 patients (65%), and placebo in 4 (28%), the difference being statistically significant (P=0.03). The dose of morphine was reduced from 313+/-52 to 174+/-33 mg/day (P < 0.001) in the nimodipine group, and from 254+/-26 to 218+/-19 mg/day (not significant) in the placebo group. The percentages of reduction in the daily dose of morphine also showed significant differences between both groups (P=0.02). One week after introducing nimodipine or placebo, while the dose of morphine remained similar to that of the pre-test week, the serum levels of morphine and its glucuronides were not modified significantly. We conclude that the introduction of nimodipine in patients chronically treated with morphine may be a safe alternative to reduce the daily requirements of the opioid. It is suggested that interference with Ca2+-related events may attenuate the development and/or expression of tolerance to morphine in a clinically relevant way.

The oestrogenic effects of gestodene, a potent contraceptive progestin, are mediated by its A-ring reduced metabolites.

Gestodene (17 alpha-ethynyl-13 beta-ethyl-17 beta-hydroxy-4, 15-gonadien-3-one) is the most potent synthetic progestin currently available and it is widely used as a fertility regulating agent in a number of contraceptive formulations because of its high effectiveness, safety and acceptability. The observation that contraceptive synthetic progestins exert hormone-like effects other than their progestational activities, prompted us to investigate whether gestodene (GSD) administration may induce oestrogenic effects, even though the GSD molecule does not interact with intracellular oestrogen receptors (ER). To assess whether GSD may exert oestrogenic effects through some of its neutral metabolites, a series of experimental studies were undertaken using GSD and three of its A-ring reduced metabolites. Receptor binding studies by displacement analysis confirmed that indeed GSD does not bind to the ER, whereas its 3 beta,5 alpha-tetrahydro reduced derivative (3 beta GSD) interacts with a relative high affinity with the ER. The 3 alpha,5 alpha GSD isomer (3 alpha GSD) also binds to the ER, though to a lesser extent. The ability of the A-ring reduced GSD derivatives to induce oestrogenic actions was evaluated by the use of two different molecular bioassays: (a) transactivation of a yeast system co-transfected with the human ER alpha (hER alpha) gene and oestrogen responsive elements fused to the beta-galactosidase reporter vector and (b) transactivation of the hER alpha-mediated transcription of the chloramphenicol acetyl transferase (CAT) reporter gene in a HeLa cells expression system. The oestrogenic potency of 3 beta GSD was also assessed by its capability to induce oestrogen-dependent progestin receptors (PR) in the anterior pituitary of castrated female rats. The results demonstrated that 3 beta GSD and 3 alpha GSD were able to activate, in a dose-dependent manner, the hER alpha-mediated transcription of both the beta-galactosidase and the CAT reporter genes in the yeast and HeLa cells expression systems respectively. In both assays the 3 beta derivative of GSD exhibited a significantly greater oestrogenic effect than its 3 alpha isomer, while unchanged GSD and 5 alpha GSD were completely ineffective. Neither 3 beta GSD nor 3 alpha GSD exhibited oestrogen synergistic actions. Interestingly, the pure steroidal anti-oestrogen ICI-182,780 diminished the transactivation induced by 3 beta GSD and 3 alpha GSD in the yeast expression system. Furthermore, administration of 3 beta GSD resulted in a significant increase of oestrogen-dependent PR in the anterior pituitaries of castrated rats in comparison with vehicle-treated animals. The characteristics of the 3 beta GSD-induced PR were identical to those induced by oestradio benzoate. The overall results demonstrate that 3 beta GSD and its 3 alpha isomeric alcohol specifically bind to the ER and possess a weak intrinsic oestrogenic activity, whereas unmodified GSD does not. The data contribute to a better understanding of the GSD mechanism of action and allow the hypothesis to be advanced that the slight oestrogenlike effects attributable to GSD are mediated by its non-phenolic, tetrahydro reduced metabolites.

In vitro metabolism of gestodene in target organs: formation of A-ring reduced derivatives with oestrogenic activity.

Gestodene (13beta-ethyl-17alpha-ethynyl-17beta-hydroxy-4,5-gonadien-3-one), the most potent progestin ever synthesized, stimulates breast cancer cell growth through an oestrogen receptor-mediated mechanism, and its use in hormonal contraception has been associated with side effects attributable to oestrogenic actions. These observations have remained controversial, since gestodene does not bind to the oestrogen receptor or exert oestrogen-like activities. Recently, we have demonstrated that non-phenolic gestodene derivatives interact with oestrogen receptors and induce oestrogenic effects in cell expression systems. To assess whether gestodene is biotransformed to metabolites with intrinsic oestrogenic potency, [3H]- and [14C]-labelled gestodene were incubated in vitro with rat anterior pituitary, hypothalamus and ventral prostate homogenates under different experimental conditions. The most remarkable finding was the isolation and identification of 3beta,5alpha-tetrahydrogestodene and 3alpha,5alpha-tetrahydrogestodene as metabolic conversion products of gestodene, presumably with 5alpha-dihydrogestodene as intermediate. The overall results seem to indicate that the weak oestrogenic effects attributable to gestodene could be mediated by its tetrahydro metabolites.

Assessment of the oestrogenic activity of the contraceptive progestin levonorgestrel and its non-phenolic metabolites.

Levonorgestrel (13beta-ethyl-17alpha-ethynyl-17beta-hydroxy-4-gonen-3-one), a potent contraceptive progestin stimulates growth and proliferation of cultured breast cancer cells through a receptor-mediated mechanism, even though levonorgestrel does not bind to the oestrogen receptor (ER). To assess whether the oestrogen-like effects induced by this synthetic progestin are exerted via its metabolic conversion products, we studied the binding affinity of three A-ring levonorgestrel derivatives to the ER and their capability to transactivate an oestrogen-dependent yeast system co-transfected with the human ER gene and oestrogen responsive elements fused to a beta-galactosidase reporter vector. The results demonstrated that the 3beta,5alpha reduced levonorgestrel derivative and to a lesser extent its 3alpha isomer interact with the oestrogen receptor, with a significantly lower relative binding affinity (2.4% and 0.4%, respectively) than that of oestradiol (100%), while levonorgestrel does not. Both levonorgestrel metabolites were able to activate, in a dose-dependent manner, the beta-galactosidase reporter gene in the yeast expression system, an effect that was precluded by a steroidal antioestrogen. The oestrogenic potency of levonorgestrel metabolites was significantly lower (750-fold) than that of oestradiol. Furthermore, high doses of 3beta,5alpha levonorgestrel (2.5 mg/day/6 days) induced an increase of oestrogen-dependent progestin receptor in the anterior pituitary of castrated rats. The overall data offer a plausible explanation for the weak oestrogenic effects induced by high, non-pharmacological doses of levonorgestrel.

Mass treatment against human taeniasis for the control of cysticercosis: a population-based intervention study.

An intervention study with mass treatment against taeniasis to prevent neurocysticercosis due to Taenia solium in a rural community in Mexico was performed in 1991-96. Information and biological samples were obtained at the beginning of the study, at 6 months and at 42 months after mass treatment with praziquantel at a single dose of 5 mg/kg. Prevalence rates of taeniasis were measured by the detection of Taenia coproantigens and Taenia eggs in faeces; neurocysticercosis was suggested by clinical data and by serum antibodies in humans and also in swine. A reduction of 53% after 6 months and of 56% after 42 months for human taeniasis was seen after treatment. Late-onset general seizures decreased 70%. Anti-cysticercus antibodies in the human population were reduced by 75% after 42 months. Antibodies in pigs also showed a significant reduction of 55% after 6 months. In conclusion, an impact of mass chemotherapy against taeniasis to control cysticercosis in the short and long term was demonstrated. Praziquantel for tapeworm treatment should not be given at doses lower than 10 mg/kg. Late-onset convulsive crisis and specific antibodies are good indicators of neurocysticercosis and of exposure to the parasite, respectively.

Characterization of the potentiation of the antinociceptive effect of diclofenac by vitamin B complex in the rat.

The role of vitamin B complex preparations as an analgesic adjuvant is controversial. Therefore, the purpose of the present study was to characterize the potentiation of the antinociceptive effect of diclofenac by a vitamin B complex preparation and its individual components by using the pain-induced functional-impairment model in the rat (PIFIR). Pain was produced by the intraarticular injection of uric acid in the right hind limb. Oral administration of diclofenac resulted in a dose-dependent antinociceptive effect. Oral administration of a vitamin B complex preparation containing thiamine (vitamin B(1)), pyridoxine (vitamin B(6)), and cyanocobalamin (vitamin B(12)) in a 1:1:0.01 proportion did not produce any antinociception by itself, but it significantly potentiated the effect of diclofenac. Coadministration of diclofenac with either thiamine or pyridoxine resulted in an antinociceptive effect similar to that of diclofenac alone. On the other hand, coadministration of cyanocobalamin significantly increased diclofenac-induced antinociception. It is concluded that the potentiation of diclofenac-induced antinociception in the PIFIR model is due to cyanocobalamin.

Evaluation of the effectiveness of Rosmarinus officinalis (Lamiaceae) in the alleviation of carbon tetrachloride-induced acute hepatotoxicity in the rat.

The effect of oral administration of Rosmarinus officinalis L. (Lamiaceae) on CCl(4)-induced acute liver injury was investigated. Rats were daily treated with the plant extract at a dose of 200 mg/kg corresponding to 6.04 mg/kg of carnosol as determined by reverse phase high-performance liquid chromatography. The treatment was initiated 1 h after CCl(4) administration and Rosmarinus officinalis fully prevented CCl(4) effect on hepatic lipid peroxidation after 24 h of CCl(4) administration. The increase in bilirubin level and alanine aminotransferase activity in plasma induced by CCl(4) was completely normalized by Rosmarinus officinalis. The treatment also produced a significant recovery of CCl(4)-induced decrease in liver glycogen content. CCl(4) did not modify the activity of liver cytosolic glutathione S-transferase (GST) compared with that of control groups. However, Rosmarinus officinalis increased liver cytosolic GST activity and produced an additional increment in plasma GST activity in rats treated with CCl(4). Histological evaluation showed that Rosmarinus officinalis partially prevented CCl(4)-induced inflammation, necrosis and vacuolation. Rosmarinus officinalis might exert a dual effect on CCl(4)-induced acute liver injury, acting as an antioxidant and improving GST-dependent detoxification systems.

[Preventive treatment of primary dysmenorrhea with ibuprofen]. / Tratamiento profiláctico de la dismenorrea primaria con ibuprofén.

An open, prospective study, including 15 young women with primary dysmenorrhea was carried out to asses the prophylactic administration of Ibuprofen for the treatment of severe and disabling primary dysmenorrhea. The study lasted six months, representing a total of 90 cycles, the inclusion criteria were: 1) severe and disabling primary dysmenorrhea, 2) Failure with previous conventional treatments, 3) regular menstrual cycles, 4) without active sexual life, 5) voluntary participation. The treatment schedule included 400 mg of ibuprofen every 8 hours, starting 24 hours before the menstrual cycle during 4 days of menstruation for six consecutive cycles. The intensity of the pain was recorded every eight hours using a linear analogue scale from 0 to 10 where 0 was absence of pain and 10 was severe or disabling pain. Results showed that the mean of initial intensity of the menstrual cramp experienced in the cycle before the treatment (control) was 9.47 +/- 0.5. During the prophylactic treatment the means of initial intensity of the pain were significantly lower, between 7.84 +/- 0.37 and 7.21 +/- 0.52. A statistically significant progressive decrease of pain was recorded during the duration of treatment. After 48 hours of treatment the intensity of the pain was recorded as three (mild). We conclude that the prophylactic administration of ibuprofen is an effective treatment for selected women experiencing severe and disabling primary dysmenorrhea.

Alternating chemotherapy: gemcitabine and cisplatin with concurrent radiotherapy for treatment of advanced head and neck cancer.

BACKGROUND: Many studies have shown gemcitabine and cisplatin are radiosensitizers. Concurrent chemoradiation seems to be an efficient approach for treatment of advanced head and neck cancer (HNC), but toxicity is significant. OBJECTIVE: To evaluate safety and explore efficacy of alternating chemotherapy with gemcitabine and cisplatin concurrent with radiotherapy in patients with advanced non-metastatic HNC. PATIENTS AND METHODS: Twenty-eight patients diagnosed with advanced Squamous Cell Carcinomas of the Head and Neck (SCCHN) in stages III (28%), IVa (36%), and IVb (36%) were treated with gemcitabine: 100mg/m(2) alternating with cisplatin: 50mg/m(2) concurrent with radiotherapy at doses of 2 Gy/day until completing 70 Gy. While awaiting for concurrent treatment, eleven patients received induction chemotherapy with cisplatin: 100mg/m(2) and 5-FU: 1000 mg/m(2). Toxicity, especially in relation to mucositis, xerostomy, dysphagia, leucopenia and radiodermitis was evaluated. RESULTS: 5-year progression-free survival was 27.8 ± 17.2% (CI-95: 0-61.5) and overall survival was 55.9 ± 11% (CI: 34.4-77.5). Overall response rate was 93%; complete response was 64.3% and partial response was 28.6%. Extensive surgery for primary site was avoided in 19 patients (70.4%). Grade 3-4 adverse events were mucositis (46.4%), leucopenia (14.2%), dysphagia (25%), xerostomy (10.7%) and radiodermitis (3.6%). Response rates and toxicity were not significantly different among those patients with and without induction chemotherapy, but survival was higher in patients receiving induction. CONCLUSIONS: Gemcitabine alternating with cisplatin concurrent with radiotherapy is an active and safe treatment that deserves further study.

Effects of alpha-tocopherol on oxidative status and metabolic profile in overweight women.

Despite extensive research, the effects of alpha-tocopherol supplementation remain controversial. Few studies have been focused on obese and overweight people. We examined the effects of alpha-tocopherol (AT) on the oxidative status and metabolic profile in overweight women. Sixteen overweight women between the ages of 40-60 years old, received AT, 800 IU/day during 12 weeks, followed by a 6-week washout period. Blood samples were taken at the beginning and then every 6 weeks until the end of the study. AT, retinol, malondialdehyde (MDA), total antioxidant status (TAS), selenium-dependent glutathione peroxidase (GPx) and CuZn-superoxide dismutase (SOD) were quantified to evaluate the oxidative stress. The metabolic profile was estimated by measuring glycated hemoglobin (HbA1c) in erythrocytes and glucose, phosphate, magnesium, lipid and lipoprotein concentrations in serum. Under AT administration HbA1c, serum- MDA levels and erythrocyte GPx activity were markedly reduced. TAS, AT and Mg2+ concentrations in serum and SOD activity in erythrocytes were higher after AT treatment. Body weight; glucose, lipid and retinol concentrations, or blood cells count were unchanged. Lipid peroxidation was considerably reduced in AT treated women and also improved serum antioxidant status was observed, but the imbalanced response between erythrocyte SOD and GPx activities could affect normal response to oxidative stress.

Preparation of seven- and eight-membered boron heterocycles from different salen ligands and arylboronic acids.

Arylboronic acids and different salen ligands have been brought to reaction in a 2:1 stoichiometry in ethanol, toluene, and acetonitrile. In all cases bimetallic boronates with chiral boron atoms could be isolated with the difference that in ethanol mostly open bimetallic boronic esters are obtained, while in toluene or acetonitrile closed bimetallic complexes with a central seven- or eight-membered heterocyclic ring are formed. Both structural types have been characterized by spectroscopic techniques and X-ray crystallography showing that the reactions are diastereoselective in the case of the bimetallic heterocyclic structures. The configurations and conformations of the seven- and eight-membered rings are different, and this may depend on steric effects and/or repulsive intramolecular pi-pi interactions between the two salicylidene moieties attached to the central ring.

[Comparative study between bisoprolol and metoprolol, combined with hydrochlorothiazide, as antihypertensive therapy]. / Estudio comparativo entre bisoprolol y metoprolol, asociados a hidroclorotiazida, como terapia antihipertensiva.

The main objective of this research was to compare the efficacy and security of bisoprolol (B), a new cardioselective beta-blocker, that does not have intrinsic sympathomimetic activity, and metoprolol associated to hydrochlorothiazide (HCTZ), in the treatment of patients with mild to moderate hypertension. Sixty-two hypertensive patients (47 females and 15 males) aged 20 to 70 years (mean 52.5 +/- 10.4) were included in a double-blind, placebo controlled and randomized clinical trial. After a two-weeks wash out period and a similar placebo phase, patients were randomly assigned to receive either a once-daily dosing of B (10 mg) with 6.25 mg of HCTZ, or M (100 mg) plus 6.25 mg of HCTZ during four-weeks. If there was no reduction below 90 mmHg at the end of this period, the dosing of either beta-blocker was doubled. After eight weeks of treatment, the mean decreases in systolic/diastolic blood pressures from baseline were 31.8/21.2 and 28.0/20.6 mmHg for B/HCTZ and M/HCTZ, respectively (p < 0.0001). There were no clinically significant changes from baseline in laboratory parameters in either group. Reduction in blood pressure with B/HCTZ is associated with adverse events and metabolic changes similar to those observed with other antihypertensive drugs.

Prevalence of molecular mechanisms of resistance to azole antifungal agents in Candida albicans strains displaying high-level fluconazole resistance isolated from human immunodeficiency virus-infected patients.

Molecular mechanisms of azole resistance in Candida albicans, including alterations in the target enzyme and increased efflux of drug, have been described, but the epidemiology of the resistance mechanisms has not been established. We have investigated the molecular mechanisms of resistance to azoles in C. albicans strains displaying high-level fluconazole resistance (MICs, > or =64 microg/ml) isolated from human immunodeficiency virus (HIV)-infected patients with oropharyngeal candidiasis. The levels of expression of genes encoding lanosterol 14alpha-demethylase (ERG11) and efflux transporters (MDR1 and CDR) implicated in azole resistance were monitored in matched sets of susceptible and resistant isolates. In addition, ERG11 genes were amplified by PCR, and their nucleotide sequences were determined in order to detect point mutations with a possible effect in the affinity for azoles. The analysis confirmed the multifactorial nature of azole resistance and the prevalence of these mechanisms of resistance in C. albicans clinical isolates exhibiting frank fluconazole resistance, with a predominance of overexpression of genes encoding efflux pumps, detected in 85% of all resistant isolates, being found. Alterations in the target enzyme, including functional amino acid substitutions and overexpression of the gene that encodes the enzyme, were detected in 65 and 35% of the isolates, respectively. Overall, multiple mechanisms of resistance were combined in 75% of the isolates displaying high-level fluconazole resistance. These results may help in the development of new strategies to overcome the problem of resistance as well as new treatments for this condition.