Search PubMed⌕ Search

Biomedical subjects

A Rojas

Publications and source records attributed to A Rojas.

At least 127 records · Page 7Linked to original sources
PubMed1992

Enhancement of tumor radiosensitivity and reduced hypoxia-dependent binding of a 2-nitroimidazole with normobaric oxygen and carbogen: a therapeutic comparison with skin and kidneys.

To evaluate the therapeutic potential of normobaric oxygen and carbogen as hypoxic-cell sensitizers, both radiosensitization in a mouse mammary carcinoma, mouse skin and kidneys, and the reduction in the proportion of hypoxic tumor cells were quantified in mice breathing air, oxygen, or carbogen. Local tumor control, acute skin reactions, reduced renal clearance, and hematocrit were used as assays. X rays as 10 fractions in 5 days were given to skin and tumors and 10F/12 days to kidneys. In the tumor study, the pre-irradiation breathing time was varied from 2 to 20 min. Hypoxic cells, before and during a 10F/5 day schedule, were quantified using a 2-nitroimidazole with a theophylline side chain. Bioreductively reduced metabolites of this probe were localized in hypoxic cells that were then stained using an immunofluorescent technique and analyzed by flow cytometry. The fraction of cells with high fluorescence intensity was 19% in air, 9% in oxygen, and 3% in carbogen-breathing mice. For all three gases, hypoxia-dependent binding was similar in non-irradiated tumors and those treated with four or nine fractions. Both gases significantly enhanced tumor radiosensitivity (ER = 1.3 to 1.6) and carbogen was slightly more effective than oxygen. With carbogen, maximum sensitization was observed with a 5 min pre-irradiation breathing interval. With oxygen, pre-irradiation breathing times of 2-20 min gave similar sensitization. In skin an enhancement ratio of 1.2 was observed, whereas enhancement ratios for both renal endpoints were significantly lower (1.0 to 1.07). Relative to both tissues, there was therefore a substantial therapeutic gain by irradiating CaNT tumors under both gases, especially with carbogen.

Administration, Inhalation↗
PubMed1992

Screening for antimicrobial activity of crude drug extracts and pure natural products from Mexican medicinal plants.

Preliminary antimicrobial screening against Candida albicans and selected Gram-positive and Gram-negative bacteria of methanol extracts prepared from eight Mexican medicinal plants, noted for their antiseptic properties, was conducted. The significant activity exhibited for extracts of Ratibida latipalearis, Teloxys graveolens, Dodonaea viscosa, Hyptis albida, H. pectinata, H. Suaveolens and H. verticillata tends to support their traditional use as anti-infective agents. Only the extract of Hintonia latiflora was inactive. The antimicrobial activities of 44 pure natural compounds and two derivatives were determined. Of these, only 23 compounds were effective in inhibiting the growth of the tested organisms (MIC less than or equal to 100 micrograms/ml).

Anti-Bacterial Agents↗
PubMed1992

Generation of murine triomas secreting bi-specific monoclonal antibodies that recognize HBsAG ad and ay subtypes.

We report the generation of murine triomas by fusing splenocytes from mice previously immunized with HBsAg ay-subtype and a hybridoma, secreting anti-HBsAg ad-subtype monoclonal antibody, which was rendered HGPRT- by induced mutagenesis with N-methyl-N'nitro-N-nitrosoguanidine. The fusion yielded a 83.8% of hybrids showing the antigen specificity of the parental hybridoma and a 16.1% of bi-specific monoclonal antibodies. One of them, coded as 1C8A5, showing a heavy chain isotype (IgG1/IgG2b) was used as capture reagent in an ultramicro-ELISA. As little as 0.78 I.U. of both HBsAg ad- and ay-subtypes could be realiably detected.

Animals↗
PubMed1992

A test of equal effect per fraction in the kidney of the mouse.

Measurements of renal damage in the mouse were made to determine if there was an equal effect per fraction during a course of repeated 240-kVp X-ray doses. An X-ray dose of 2 Gy was given 2, 8, 14, or 20 times with interfraction intervals of 12 h. Some animals were also irradiated with twenty 2-Gy doses using a 5-h interfraction interval. The underlying effect per fraction (-logeSF of the notional target cell population) was determined from the additional top-up dose of d(4)-Be neutrons needed to produce measurable renal impairment assessed by decreased clearance from the plasma of [51Cr]EDTA and by a reduction in the hematocrit at 25, 29, 33, and 39 weeks after treatment. There was no significant influence of the time of assay on the values of underlying effect measured. A mean value of underlying effect was therefore calculated for the two different assays of each mouse, from the measurements at the four times. This gave approximately 40 estimates (one for each animal assessed) with each assay of the effectiveness of 2-Gy fractions in each of the four fractionation schedules, a total of 321 determinations in the study with 12-h intervals. Regression analysis showed that there was no significant trend in underlying effect per fraction with number of fractions, i.e., the damage per fraction was constant regardless of the number of fractions used. With underlying effect normalized to 1 unit of damage for a single 2-Gy dose, the slope of this plot was -0.0013 per fraction2 +/- 0.0097 (95% CL). The assumption of equal effect per fraction was therefore not invalidated in the kidney of the mouse. With a 5- instead of a 12-h interfraction interval, the 20-fraction schedule was 7% more effective as measured by the two assays analyzed together; this was significant at P = 0.0001. This shows that 5 h is not sufficient time between fractions for full repair to occur in the kidney, and underlines the need for intervals of at least 6 h between the doses in clinical radiotherapy using more than one fraction per day. The data are consistent with an alpha/beta ratio approximately 1.6 Gy, with a repair half-time approximately 1.3 h. However, these experiments were not designed to determine these parameters and their values should be regarded only as rough estimates.

Animals↗
PubMed1991

[Evaluation of IgG and IgA type antibodies to capsid and early antigens of the Epstein-Barr virus in the diagnosis of nasopharyngeal carcinoma].

BACKGROUND: The Epstein-Barr virus (EBV) is related with nasopharyngeal carcinoma (NPC) in that, in this neoplasm, high levels of antibodies are found vs different EBV antigens. METHODS: The determinations of IgG and IgA type antibodies were evaluated vs capsid antigens (VCA) and early antigen (EA) of the EBV by indirect immunofluorescence in 14 patients diagnosed with NPC, in 12 patients with other tumors of the head and neck and in 61 blood donors. RESULTS: The detection of IgA type antibodies with a sensitivity and specificity of 100% and 92% for the VCA antigen and of 86% and 100% for the EA antigen are the most useful tests in the early diagnosis of nasopharyngeal carcinoma. The determination of IgG type antibodies were of a more limited usefulness with sensitivities and specificities of 86% and 67% for IgG anti-VCA and 100% and 83% of IgG anti-EA. CONCLUSIONS: The detection of antibodies vs VCA and EA antigens is useful in the differential diagnosis of NPC with other tumors of the head and neck.

Adult↗
PubMed1991

A therapeutic benefit from combining normobaric carbogen or oxygen with nicotinamide in fractionated X-ray treatments.

The ability of normobaric oxygen and carbogen (95% O2 + 5% CO2) combined with nicotinamide to enhance the radiosensitivity of two rodent adenocarcinomas and of mouse skin and kidneys, using a 10 fraction radiation schedule, was compared with the effect of radiation in air with and without the drug. Tumour response was assayed using local control and regrowth delay, and compared with acute skin reactions, decreased renal 51Cr-EDTA clearance and reduction in haematocrit. Nicotinamide increased the radiation sensitivity of CaNT tumours under all three different oxygen concentrations tested (21, 95 and 100% oxygen). The effect was statistically significant for oxygen and carbogen but not for air; the combination of nicotinamide with carbogen gave the greatest increase in tumour radiosensitivity. Relative to treatments in air without the drug, the enhancement ratios (ER) at the TCD50 level were 1.17, 1.65 and 1.83 for CaNT tumours irradiated in air, oxygen or carbogen and injected with nicotinamide 1 h before each fraction. The ER in CaRH tumours irradiated in carbogen plus the drug was 1.83, which was greater, but statistically not significantly different, to that seen with carbogen alone (ER = 1.68). In skin, relative to air without the drug, the increase in radiosensitivity by nicotinamide was greater in oxygen and carbogen than in air (1.29, 1.36 and 1.08, respectively). The ERs for both assays of renal damage were similar and lower than those in skin: less than or equal to 1.07, less than or equal to 1.13 and less than or equal to 1.16 for irradiations done in air, oxygen and carbogen plus nicotinamide, relative to air alone. A comparison of these results in the tumours and normal tissues showed that a significant therapeutic benefit was obtained with normobaric oxygen and carbogen combined with nicotinamide. This benefit is greater than observed with other radiosensitizers tested so far. Toxic side effects of the treatment are unlikely in a clinical situation, since prolonged administration of nicotinamide is well tolerated in man. The combination of normobaric carbogen with nicotinamide could be an effective method of enhancing tumour radiosensitivity in clinical radiotherapy where hypoxia limits the outcome of treatment.

Adenocarcinoma↗
PubMed1991

Influence of circadian rhythms on radiosensitivity: single and fractionated dose studies in mouse skin.

In rodent skin significant increases in labelling and mitotic indices have been reported during the period of maximum nocturnal activity. It has been suggested that sparing of radiation damage in fast-proliferating normal tissues could be achieved if treatments were given at the time of day when the maximum number of normal cells were most radioresistant. If changes in radiosensitivity do occur in tissues with circadian fluctuations in the cell kinetic parameters, then the magnitude of these changes should be dependent on the size of dose per fraction. Because of the implications for clinical radiotherapy, especially in regimes where multiple fractions per day are given (MFD), possible diurnal variations in radiosensitivity were investigated using single dose and fractionated X-ray regimens (5F/5 days, 8F/8 days), in rodent skin. Treatments were delivered at 1, 3, 5 a.m. (time of highest DNA synthetic activity in mouse epidermis), 6 and 7 a.m. (highest mitotic activity) and at 5 p.m. (minimum labelling and mitotic indices). To investigate a large range of doses per fraction, fractionated X-rays were given alone or followed by neutron top-up doses. Using a range of doses per fraction of 30 Gy down to 1 Gy, we did not detect any change in radiosensitivity with any of the schedules. Our results suggest that a decrease in normal tissue tolerance is unlikely to be observed in patients even if irradiated at a time of day at which a maximum increase in radiosensitivity might be predicted on the basis of a high mitotic index.

Animals↗
PubMed1991

Recovery kinetics of X-ray damage in mouse skin: the influence of dose per fraction.

The rate of recovery from radiation damage, as a function of dose per fraction, was investigated in mouse skin. Two different experimental designs were used, both incorporating the neutron top-up technique which enables the X-ray dose per fraction to be kept constant whilst changing the interfraction interval. Either equally spaced X-ray fractions (concertina design) or single or multiple pairs of X-ray doses (single and multiple split-dose designs) were given at varying intervals, followed by graded doses of neutrons. A wide range of X-ray doses per fraction were investigated (from 1 to 10.5 Gy) and the data were analysed using the Thames Incomplete Repair (IR) model modified for use with neutron top-up doses. Analyses of the data, obtained from five different experiments, indicate that the rate of recovery from radiation damage is significantly faster at doses per fraction between 1 and 4.4 Gy than at 10.5 Gy. These data appear not to support the assumption, made by most recovery models, that the rate of recovery is independent of dose.

Animals↗
PubMed1991

Response of the mouse mediastinum to single and fractionated X-rays.

The acute oesophageal response, after localized mediastinal irradiation in unanaesthetized mice, was assessed with a sequential, non-invasive and clinically orientated assay. Changes in body weight, after single and fractionated X-ray doses (8 fractions in 8 or 15 days and 4 fractions in 4 or 13 days), were recorded and the nadir of weight loss for each regime was used as the end-point. In our studies, quantal and non-quantal analyses of the weight loss data gave good dose-response relationships. The shapes of the dose-effect curves for single doses, 4F/4 days and 8F/8 days showed a remarkable degree of radioresistance, which became less apparent when the overall time was increased to 13 and 15 days for 4 and 8 fractions, respectively. The alpha/beta values (7-17 Gy) are within the range found for other acutely responding normal tissues. Histopathological changes were also assessed and the structural changes observed in the oesophageal epithelium, after a single dose of 34 Gy or after 46 Gy given as 3F/6 days, correlated with the gross changes observed in body weight.

Animals↗
PubMed1991

[Polycystic ovary syndrome as expression of 3-beta-hydroxysteroid dehydrogenase deficiency].

Late-onset adrenal enzymatic deficiencies are a common cause of hirsutism. They can produce a PCO syndrome-like clinical course, underscoring the multi-causality of this condition. We report a 18 year old woman with secondary amenorrhea and hirsutism, whose serum levels of testosterone and DHEA-S were 175 ng/dl and 7.3 micrograms/ml and the LH/FSH ratio was 5.9. Dexamethasone decreased testosterone and DHEA-S levels, while the ACTH stimulation test increased the 17 hydroxypregnenolone serum concentration and the 17 hydroxypregnenolone/17 hydroxyprogesterone ratio to values considered diagnostic of 3 beta hydroxysteroid dehydrogenase deficiency.

3-Hydroxysteroid Dehydrogenases↗
PubMed1991

[Evaluation of 2 serological techniques in the diagnosis of neurocysticercosis: complement fixation reaction and Western blot].

Evaluation of two serological techniques for diagnosis cysticercosis: complement fixation reaction and Western blot. Comparative study that includes 49 sera samples and 30 CSF samples belonging to 35 patients with clinical diagnosis of cysticercosis of the CNS. As a control group we used 10 sera samples of patients with Trichinella spiralis infection, 33 sera samples of patients with hydatid cyst disease, 9 sera samples from patients with oxyuriasis, 52 sera samples of healthy blood donors and 22 additional CSF samples from patients with different CNS disorders. Thirty-one samples were positive by Western blot technique and 21 samples by complement fixation reaction technique. Agreement between both techniques was 76%. Gathering clinical and laboratory information we believe that a total of 11 patients had cysticercosis of the CNS (33 samples), and three additional patients remain with indeterminate diagnosis. We have also detected cross-reactions with Western blot techniques (reactivity to more than one band) in 43% of patients with hydatid disease and in 20% of patients with Trichinella spiralis infection, but none in oxyuriasis patients. The CFR technique had cross-reaction with 33% of sera samples from hydatid disease patients and 20% of those from oxyuriasis patients. No cross-reactions were seen in any of control patients with both techniques. The two different techniques tested can be of help, together with clinical and radiology data, in the diagnosis of cysticercosis of the CNS. However, both techniques showed strong cross-reactions with hydatid disease.

Animals↗
PubMed1991

[Survey about smoking among third-year medical students at the National University of Cordoba].

A survey about smoking was done at the Second Department of Pathology at the National University of Córdoba. The results of a questionnaire answered by 70% of 520 students were as follows: 23% of the students smoke (29% of the males and 17% of the females). The generation of these students smoke much less than that of their parents (70% of the male parents and 25% of the female parents smoke). The family groups are fairly well informed about cigarette danger for health. Nevertheless, in a significant number of cases children and pregnant women are subjected to passive smoking and to a lesser extent pregnant women smoke themselves. It is difficult to quit smoking. Many tried it without results. 80% of students are against smoking in closed places. The majority of students claim to respect the right of non smokers. Few of the Departments of Basic Sciences teach about smoking and several members of the teaching staff smoke during academic activities and/or permit students to smoke. This meets the disapproval of the great majority of the students which view this as a bad example and something in contradiction with the expected role of teachers. We hope smokers will respect the right of non smokers and also respect the rules about smoking of our University.

Adult↗
PubMed1991

Repopulation in murine skin after X-ray treatments with multiple fractions per day.

The kinetics of repopulation of clonogens in skin after fractionated X-ray exposures was studied in a series of experiments using a top-up design. The feet of mice were exposed to small X-ray doses (1.5 or 2 Gy), given two or three times a day on consecutive days with a minimum interfraction interval of 8 h. A single top-up dose of d(4)-Be neutrons was then given at various intervals after the last X-ray fraction, typically on Days 1,4,8, 15, and 19. The acute skin reaction produced was scored an analyzed by both a standard 23-day averaging and a 7-day averaging procedure. Either method gave similar results and led to the same conclusions. The amount of top-up dose needed to produce a fixed skin reaction was used as a measure of the net effect of the X-ray treatments. This net effect is a result of the initial reduction in skin clonogens due to X rays, and their repopulation before the top-up dose was given. Repopulation was not detected during any of these courses of fractionated treatment, up to an overall time of at least 12 and possibly 16 days. On completion of X-ray schedules lasting 6-16 days, repopulation started 4 days later. In contrast, this delay lengthened to approximately 8 days for shorter overall treatment times of 3-4 days. Once repopulation started, it proceeded rapidly over 11 days so that by 15 days after the cessation of X rays, the skin was restored almost to its normal state with respect to radiosensitivity. The residual damage from Day 15 to Day 19 postirradiation was 3-13% of a full-effect level. The rate of repopulation can be expressed as a clonogen doubling time (Tclon), assuming that an average skin reaction of 1.5 is equivalent to a clonogen surviving fraction of 1.7 x 10(-5). Tclon varied inversely with the amount of initial damage inflicted by the X rays, with the shortest values (1-1.3 days) seen following X-ray doses that gave an initial damage level of 60-80% of full effect. These data are consistent with a hypothesis that damage is "sensed" only 10-12 days after the first X-ray fraction, which provides the stimulus for repopulation of the target cells in the basal layer, the keratinoblasts.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Inhibition of phosphoenolpyruvate carboxykinase from Trypanosoma (Schizotrypanum) cruzi epimastigotes by 3-mercaptopicolinic acid: in vitro and in vivo studies.

3-mercaptopicolinic acid (3MP) was shown to be a powerful and specific inhibitor of the phosphoenolpyruvate carboxykinase (PEP-carboxykinase; ATP:oxyloacetate carboxylyase (transphosphorylating), EC 4.1.1.49) isolated and purified to homogeneity from Trypanosoma (Schizotrypanum) cruzi epimastigotes (Urbina, J. A., 1987, Arch. Biochem. Biophys. 258, 186-195). In the presence of saturating concentrations of the cosubstrates the inhibition was purely noncompetitive toward all substrates in the carboxylation reaction. The inhibition was specific to this enzyme, being nonexistent or moderate toward eight other enzymes tested that are involved in glycolysis, hexose monophosphate shunt, Krebs' cycle, and amino acid metabolism. These facts, together with the kinetic constants of the enzyme and the intracellular concentrations of its substrates, predicted a very potent inhibition of the reaction catalyzed by this enzyme in vivo. In accordance of this prediction 200 microM 3MP inhibited 2.2-fold the production of [2,2'-13C]succinate from D-[1-13C]glucose by intact epimastigotes under anaerobic conditions, as shown by 13C NMR and 1H NMR spectroscopy; correspondingly the overall glucose consumption rate decreased by the same factor, while the relative rate of production (per mole of glucose consumed) of the other main product of glucose catabolism, [3-13C]alanine, was increased 3-fold by the drug. Under aerobic conditions the glucose catabolism was faster (negative Pasteur effect) and the drug at the same concentration again blocked succinate production but had negligible effects on glucose consumption. On the other hand, 200 microM 3MP blocked completely the epimastigotes' catabolism of L-[U-14C]proline through the Kreb's cycle via PEP-carboxykinase, as indicated by the disappearance of 14C label present in alanine, pyruvate, citrate, and isocitrate after 1 h of incubation in the presence of the labeled amino acid, while the amount of radioactivity present in alpha-ketoglutarate and malate doubled. The results support the proposition that PEP-carboxykinase has a central role in the energy metabolism of this organism as it is essential for the catabolism of amino acids.

Anaerobiosis↗