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Biomedical subjects

R Rios

Publications and source records attributed to R Rios.

At least 19 recordsLinked to original sources
PubMed2005

Increased sperm DNA damage in patients with varicocele: relationship with seminal oxidative stress.

BACKGROUND: The pathophysiology of the testicular damage in varicocele has not been completely understood. Oxidative stress and related sperm DNA damage have been identified as significant causes of male infertility. The current study was designed to determine the extent of sperm nuclear DNA damage in patients with varicocele and to examine its relationship with oxidative stress. METHODS: Semen samples from 55 patients with clinical varicocele and 25 normozoospermic donors were examined. Varicocele sperm samples were classified as normal or abnormal according to World Health Organization guidelines. Sperm DNA damage was evaluated by the sperm chromatin structure assay/flow cytometry and by the terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) assay. Levels of reactive oxygen species (ROS) and total antioxidant capacity were assessed by a chemiluminescence assay. RESULTS: DNA fragmentation index (DFI) (percentage of sperm with denatured DNA) values and the percentage of TUNEL-positive cells were significantly greater in patients with varicocele, either with normal (DFI, 20.7 +/- 4.0; TUNEL positive, 26.1 +/- 3.2) or with abnormal (DFI, 35.5 +/- 9.0; TUNEL positive, 32.2 +/- 4.1) semen profile, compared with controls (DFI, 7.1 +/- 0.9; TUNEL positive, 14.2 +/- 1.2). Similarly, ROS levels were significantly higher (P < 0.01) in both groups of patients with varicocele. CONCLUSIONS: The presence of a varicocele is associated with high levels of DNA-damage spermatozoa even in the presence of normal semen profile. The results also indicate that oxidative damage is associated with sperm DNA damage in these patients.

Biomarkers↗
PubMed2005

Investigation of human contacts: a Mycobacterium bovis outbreak among cattle at a California dairy.

BACKGROUND: In May 2002, a Mycobacterium bovis outbreak occurred among cattle at a California dairy. We investigated to determine whether persons were infected after working with the cattle or drinking their raw milk. METHODS: We identified persons with potential contact with infected cattle, including dairy workers, their family members, and slaughterhouse workers. Persons were given a tuberculin skin test (TST), and their occupational and milk-drinking habits were recorded. RESULTS: Of 88 potential contacts, 78 (90%) were given a TST; 33 (43%) had positive TST results, of whom 32 were Mexican-born (RR 15.8, 95%CI 2.3-108.8). No persons had active tuberculosis. Eighteen (72%) dairy workers, 11 (27%) family members, and four (33%) slaughterhouse workers had positive TST results. After adjusting for Mexican-birth and age, dairy workers were no more likely to have positive TST results than others (adjusted RR 1.2, 95%CI 0.6-2.1). Forty-one (62%) dairy staff and their family members drank raw milk from the dairy; 21 (51%) had positive TST results and were Mexican-born. All 13 US-born raw milk drinkers had negative TST results. CONCLUSION: A high prevalence of positive TST results was documented among workers at the affected dairy, although results were not independently associated with contact with infected cattle or milk products. Further assessment of California dairy workers should be considered.

Agricultural Workers' Diseases↗
PubMed2001

Validated high-performance liquid chromatographic assay for simultaneous determination of dacarbazine and the plasma metabolites 5-(3-hydroxymethyl-3-methyl-1-triazeno)imidazole-4-carboxamide and 5-(3-methyl-1-triazeno)imidazole-4-carboxamide.

Dacarbazine (DTIC) is a prodrug that is clinically effective in the treatment of Hodgkin's disease, melanoma and soft tissue sarcoma. To better characterize the clinical pharmacology of parent drug and reactive metabolites, a reversed-phase HPLC method with UV detection was developed for simultaneous determination of dacarbazine and the metabolites 5-(3-hydroxymethyl-3-methyl-1-triazeno)imidazole-4-carboxamide (HMMTIC) and 5-(3-methyl-1-triazeno)imidazole-4-carboxamide (MTIC). Chromatographic separation was achieved with a Zorbax SB-CN column and with a mobile phase of 80% 50 mM ammonium phosphate, pH 6.5, 20% methanol and 0.1% triethylamine. HMMTIC, MTIC and DTIC were extracted from plasma with methanol precipitation of the proteins. Recovery of DTIC and the metabolites from whole blood was greater than 92%. Rapid processing of whole blood, methanol extraction and storage at -70 degrees C substantially increased the stability of HMMTIC and MTIC from less than 15 min to 3 days. Precision for HMMTIC, MTIC and DTIC ranged from 3.7 to 16.3% relative standard deviation. The accuracy ranged from 101 to 114% for all three analytes. The validated assay was used to determine the pharmacokinetic data for dacarbazine and its active metabolites for human patients with recurrent glioma receiving DTIC intravenously.

Chromatography, High Pressure Liquid↗
PubMed2000

Inhibition of fungal growth on bread by volatile components from spices and herbs, and the possible application in active packaging, with special emphasis on mustard essential oil.

The effect of modified atmosphere packaging (MAP) on the most important spoilage fungi of bread was investigated. Penicillium commune, P. roqueforti, Aspergillus flavus and Endomyces fibuliger were able to grow at oxygen levels down to 0.03%, while the chalk mould E. fibuliger was capable of growing even in the presence of an oxygen absorber. High levels of carbon dioxide retarded growth but not completely. As an alternative to MAP active packaging (AP) using volatile essential oils (EO) and oleoresins (OL) from spices and herbs were tested against a range of fungi commonly found on bread. Concentrations of 1, 10 or 100 microl EO or OL were added to a filter paper placed in the lid of a Petri dish inoculated with one of the test fungi. The Petri dish was sealed hermetically to avoid the exchange of gases. Mustard essential oil showed the strongest effect. Cinnamon, garlic and clove also had high activity, while oregano oleoresin only inhibited growth weakly. Vanilla showed no inhibitory effect towards the tested microorganisms at the applied concentrations. A. flavus was more resistant than the other microorganisms while P. roqueforti was the most sensitive. Mustard essential oil was investigated in greater detail. The minimal inhibitory concentration (MIC) for the active component, allyl isothiocyanate (AITC), was determined for the same species and an additional three moulds and one yeast. MIC values ranged from 1.8 to 3.5 microg/ml gas phase. Results showed that whether AITC was fungistatic or fungicidal depended on its concentration, and the concentration of spores. When the gas phase contained at least 3.5 microg/ml, AITC was fungicidal to all tested fungi. Results of sensory evaluation showed, that hot-dog bread was more sensitive to AITC than rye bread. The minimal recognisable concentration of AITC was 2.4 microg/ml gas phase for rye bread and between 1.8 and 3.5 microg/ml gas phase for hot-dog bread. These findings showed that the required shelf-life of rye bread could be achieved by active packaging with AITC. Active packaging of hot-dog bread, may nevertheless require the additional effect of other preserving factors to avoid off-flavour formation

Anaerobiosis↗
PubMed2000

Effect of 6-aminonicotinamide and other protein synthesis inhibitors on formation of platinum-DNA adducts and cisplatin sensitivity.

The present study was undertaken to examine the mechanistic basis for the recent observation that the pyridine nucleotide derivative 6-aminonicotinamide (6AN, NSC 21206) enhances the accumulation and resulting cytotoxicity of cisplatin in a variety of tumor cell lines. When A549 lung cancer cells or K562 leukemia cells were treated with 62.5 microM 6AN for 21 h and then pulse-labeled with [(35)S]methionine for 1 h, increased labeling of five polypeptides, one of which corresponded to a M(r) approximately 78,000 glucose-regulated protein (GRP78), was observed. Two subsequent observations, however, suggested that up-regulation of these polypeptides was unlikely to explain the interaction between 6AN and cisplatin: 1) the concentration of 6AN required to induce GRP78 was 4-fold higher than the dose required to sensitize cells to cisplatin; and 2) simultaneous treatment of cells with 6AN and cycloheximide prevented the increase in GRP78 but not the sensitizing effect of 6AN. On the contrary, treatment with the protein synthesis inhibitors cycloheximide, anisomycin, or puromycin as well as prolonged exposure to the RNA synthesis inhibitor actinomycin D mimicked the biochemical modulating effects of 6AN on cisplatin action. Conversely, 6AN inhibited protein synthesis, whereas 18 6AN analogs that failed to enhance Pt-DNA adducts and cisplatin cytotoxicity failed to inhibit protein synthesis. These observations are consistent with a model in which 6AN and other inhibitors of protein synthesis act as modulating agents by increasing cisplatin accumulation, thereby enhancing the formation of Pt-DNA adducts and subsequent cisplatin-induced cell death.

6-Aminonicotinamide↗
PubMed1999

Murine pharmacokinetics of 6-aminonicotinamide (NSC 21206), a novel biochemical modulating agent.

The pyridine nucleotide 6-aminonicotinamide (6AN) was shown recently to sensitize a number of human tumor cell lines to cisplatin in vitro. The present studies were undertaken to compare the drug concentrations and length of exposure required for this sensitization in vitro with the drug exposure that could be achieved in mice in vivo. Human K562 leukemia cells and A549 lung cancer cells were incubated with 6AN for various lengths of time, exposed to cisplatin for 1-2 hr, and assayed for Pt-DNA adducts as well as the ability to form colonies. K562 cells displayed progressive increases in Pt-DNA adducts and cisplatin sensitivity during the first 10 hr of 6AN exposure. An 18-hr 6AN exposure was likewise more effective than a 6-hr 6AN exposure in sensitizing A549 cells to cisplatin. HPLC analysis of 6AN and its metabolite, 6-amino-NAD+, permitted assessment of exposures achieved in vivo after i.v. administration of 10 mg/kg of 6AN to CD2F1 mice. 6AN reached peak serum concentrations of 80-90 microM and was cleared rapidly, with T1/2alpha and T1/2beta values of 7.4 and 31.3 min, respectively. Bioavailability was 80-100% with identical plasma pharmacokinetics after i.p. administration. At least 25% of the 6AN was excreted unchanged in the urine. The metabolite 6-amino-NAD+ was detected in perchloric acid extracts of brain, liver, kidney, and spleen, but not in serum. Efforts to prolong systemic 6AN exposure by administering multiple i.p. doses or using osmotic pumps resulted in lethal toxicity. These results demonstrated that 6AN exposures required to sensitize tumor cells to cisplatin in vitro are difficult to achieve in vivo.

6-Aminonicotinamide↗
PubMed1999

Effect of the formulation on the in-vitro release of propranolol from gellan beads.

Gellan gum beads of propranolol hydrochloride, a hydrophilic model drug, were prepared by solubilising the drug in a dispersion of gellan gum and then dropping the dispersion into calcium chloride solution. The droplets formed gelled beads instantaneously by ionotropic gelation. Major formulation and process variables which might influence the preparation of the beads and the drug release from gellan gum beads were studied. Very high entrapment efficiencies were obtained (92%) after modifying the pH of both the gellan gum dispersion and the calcium chloride solution. The beads could be stored for 3 weeks in a wet or dried state without modification of the drug release. Oven-dried beads released the drug somewhat more slowly than the wet or freeze-dried beads. The drug release from oven-dried beads was slightly affected by the pH of the dissolution medium. Gellan gum could be a useful carrier for the encapsulation of fragile drugs and provides new opportunities in the field of bioencapsulation.

Calcium Chloride↗
PubMed1999

Metabolic activation of dacarbazine by human cytochromes P450: the role of CYP1A1, CYP1A2, and CYP2E1.

Dacarbazine (DTIC), a widely used anticancer agent, is inactive until metabolized in the liver by cytochromes P450 to form the reactive N-demethylated species 5-[3-hydroxymethyl-3-methyl-triazen-1-yl]-imidazole-4-carboxamide (HMMTIC) and 5-[3-methyl-triazen-1-yl]-imidazole-4-carboxamide (MTIC). The modest activity of DTIC in the treatment of cancer patients has been attributed in part to lower activity of cytochromes P450 (P450) in humans when compared with rodents. Importantly, the particular P450 isoforms involved in the activation pathway have not been reported. We now report that the DTIC N-demethylation involved in MTIC formation by human liver microsomes is catalyzed by CYP1A1, CYP1A2, and CYP2E1. The most potent inhibitors of DTIC N-demethylation were alpha-naphthoflavone (CYP1A1 and CYP1A2), quercetin (CYP1A2), chlorzoxazone (CYP1A2 and CYP2E1), and di-sulfiram (CYP2E1). Antihuman CYP1A2 antiserum also inhibited DTIC N-demethylation. DTIC N-demethylation in a panel of 10 human liver microsome preparations was correlated with the catalytic activities for CYP1A2 (ethoxyresorufin O-deethylation and caffeine N3-demethylation) in the absence of alpha-naphthoflavone and with the catalytic activities for CYP2E1 (chlorzoxazone 6-hydroxylations) in the presence of alpha-naphthoflavone. DTIC metabolism was catalyzed by recombinant human CYP1A1, CYP1A2, and CYP2E1. The Km (Vmax) values for metabolism of DTIC by recombinant human CYP1A1 and CYP1A2 were 595 microM (0.684 nmol/min/mg protein) and 659 microM (1.74 nmol/min/mg protein), respectively. The CYP2E1 Km value exceeded 2.8 mM. Thus, we conclude that (a) CYP1A2 is the predominant P450 that catalyzes DTIC hepatic metabolism; (b) CYP2E1 contributes to hepatic DTIC metabolism at higher substrate concentrations; and (c) CYP1A1 catalyzes extrahepatic metabolism of DTIC.

Antineoplastic Agents, Alkylating↗
PubMed1996

Postnatal development of the putative neuropeptide-Y-mediated sympathetic--parasympathetic autonomic interaction.

OBJECTIVE: Intense stellate ganglion stimulation causes a long-lasting inhibition of cardiac vagal responses in adult dogs. This inhibition is thought to result from the release of neuropeptide Y from sympathetic nerve terminals, which, in turn, blocks the release of acetylcholine from parasympathetic neurons. The purpose of this study was to characterize the developmental expression of this autonomic interaction in the dog. METHODS: We studied and compared the effects of 5-min trains of right stellate ganglion stimulation on cardiac chronotropic responses to supramaximal vagal stimulation trains in 10 neonatal dogs, 8 one-month-old puppies, 8 two-month-old puppies and 8 adult dogs. RESULTS: In the adult group, after 5 min of stellate stimulation, inhibition of the vagal chronotropic response was observed in 7 of 8 (87.5%). Inhibition was observed in 100% of the one-month-olds and in 87.5% of the two-month-olds. In contrast, in the neonates, inhibition was observed in only 4 of 10 (40%) (P < 0.05). The maximum percent inhibition of the cardiac vagal response was significantly less in the neonates than in the older puppies (P < 0.001) and adults (P < 0.01), and the summated inhibition also tended to be less in the neonates (P < 0.05 compared to one- and two-month-old puppies). Finally, in 60% of the neonates and 37.5% of all other animals vagal responses after stellate stimulation were facilitated, i.e. at least 20% greater than the pre-stellate stimulation values. CONCLUSION: The putative neuropeptide-Y-mediated, sympathetic-parasympathetic interaction is not fully expressed in the canine neonate. It appears to develop quite rapidly postnatally, being fully expressed by 1 month of age. We hypothesize that this developmental change is likely the result of maturation of sympathetic nervous system function after birth. The facilitation of the vagal chronotropic response, observed in some animals after stellate stimulation, is a new finding, and may represent yet another type of autonomic interaction.

Animals↗
PubMed1994

Postnatal maturation of the response of the canine sinus node to critically timed, brief vagal stimulation.

We have previously demonstrated that vagal phase-response curves (PRC), which characterize the effects of critically timed, brief vagal stimuli on sinus node automaticity, exhibit a fundamentally different shape in the canine newborn than in the adult. In this study we analyzed the changes in sinus cycle length in response to critically timed, brief vagal stimuli, delivered to the decentralized cervical right and left vagosympathetic trunks, in two older age groups: 14 1-mo-old puppies (ages 21-36 d), and eight 2-mo-old puppies (ages 56-62 d). Vagal PRC were constructed by plotting the magnitude (percent change) of the vagal chronotropic response as a function of the phase of the cardiac cycle at which the vagus nerve was stimulated. At 1 mo of age adult-type PRC were observed, but in only six of the puppies (43%) and only in response to right vagal stimulation. By 2 mo of age adult-type PRC were observed in seven of eight puppies (88%) in response to right vagal stimulation and in three of eight (38%) in response to left vagal stimulation. Thus, clear developmental changes in the phase dependence of the vagal chronotropic response can be tracked over the first 2 mo of life in the dog.

Animals↗
PubMed1993

Structure-activity relationship studies at the benzodiazepine receptor (BZR): a comparison of the substitutent effects of pyrazoloquinolinone analogs.

The synthesis of a series of 2-phenylpyrazolo[4,3-c]quinolin-3-one derivatives and their in vitro biological evaluation as ligands for the benzodiazepine receptor are described. The in vitro activities, as determined by an analysis of GABA shift ratios, and binding affinities of these compounds to BZR are compared in terms of the electronic, lipophilic, and steric effect changes of their substituents.

Animals↗
PubMed1993

Campylobacter jejuni adapts to aerobic metabolism in the environment.

Campylobacter jejuni, when left on blood agar for prolonged periods, was found to survive better in air than under micro-aerobic conditions. After a period of 2-3 days in air, all strains of C. jejuni examined grew freely in air on subculture, and could be further subcultured apparently indefinitely in air. This adaptation to aerobic metabolism was accompanied by a change in colony morphology and some changes in outer-membrane protein patterns, but no change in serotyping reactions. The ability to colonise mice was unaltered as was the helical morphology of growing cells. The important survival phase of C. jejuni, when outside the animal gut, involves not only a change to coccal morphology but also fundamental changes in the metabolism of the organism. These changes are likely to be relevant to techniques required for culturing C. jejuni from foods and environmental sources.

Adaptation, Physiological↗
PubMed1993

Recombinant human GM-CSF enhances T cell-mediated cytotoxic function after ABMT for hematological malignancies.

The interactions of GM-CSF with cells of lymphoid lineage are not well understood and their clinical use has been focused on the acceleration of hematopoietic recovery. However, several reports have shown that human GM-CSF can affect certain T lymphocyte in vitro cytotoxic functions. To assess whether recombinant human GM-CSF (rhGM-CSF) has a more broadly based activity in the immune system, we studied its in vivo effects on endogenously-generated killer function in patients undergoing ABMT for hematologic malignancies. Eleven patients received rhGM-CSF after ABMT: eight received rhGM-CSF as a 2-h infusion daily from days +3 to +17 and three received rhGM-CSF until reaching > 500 x 10(6)/l granulocytes. Eight patients not enrolled in the rhGM-CSF therapy protocol served as controls. Natural killer (NK) cell activity and activated killer (AK) cell activity were studied before conditioning, during rhGM-CSF therapy and after withdrawal of GM-CSF. rhGM-CSF therapy does not affect NK activity. Circulating lymphocytes with the ability to kill AK-sensitive targets appear spontaneously in control ABMT patients. AK activity was 1.6 +/- 0.8% before ABMT increasing to 9 +/- 2.5% and 14 +/- 2.1% at 2 and 3 weeks after ABMT, respectively (p = 0.002). In rhGM-CSF-treated patients this phenomenon also occurs. AK activity increased from 2.4 +/- 1.5% before ABMT to 33.6 +/- 8.1% during rhGM-CSF administration (p = 0.001) and 17.5 +/- 3.4% after withdrawal (p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Cytoplasmic male sterility is associated with large deletions in the mitochondrial DNA of two Nicotiana sylvestris protoclones.

Two cytoplasmic male-sterile plants (CMSI and CMSII) were obtained by protoplast culture in Nicotiana sylvestris. Both plants showed large deletions (up to 50 kb) in their mitochondrial DNA. Restriction maps of the reorganized regions suggested that the deletions occurred via two homologous recombination events (rec. 1 and rec. 2) in the parental mitochondrial genome. With the exception of nad5, no mitochondrial DNA polymorphism could be detected between parental and CMS lines using different heterologous genes probes. A sequence homologous to the Oenothera nad5 mitochondrial gene was located close to the CMSI-specific rec. 2 region. Moreover, a cDNA probe corresponding to total mitochondrial RNA from the parent line was found to hybridize to mitochondrial DNA fragments involved in the rec. 1 event common to both CMS lines, suggesting that rec. 1 lies in a transcribed region. Cytoplasmic male sterility in the Nicotiana sylvestris CMS mutants could be due either to gene deletion or to a regulatory effect of such a deletion on mitochondrial gene expression, rather than to the presence of specific polypeptides as has been shown in the T cytoplasm of maize, or in CMS Petunia.

Blotting, Southern↗
PubMed1992

Enterohemorrhagic Escherichia coli associated with hemolytic-uremic syndrome in Chilean children.

A clinicoepidemiological study was undertaken to determine if enterohemorrhagic Escherichia coli (EHEC) was associated with hemolytic-uremic syndrome (HUS) in children in Santiago, Valdivia, and Temuco, Chile. Prospective surveillance detected 20 hospitalized cases of HUS in children less than 4 years of age in these cities from March 1988 to March 1989. Each HUS patient was matched (by sex and age) with two control children (hospitalized elective-surgery patients). To detect EHEC, DNA from stool culture isolates of E. coli was detected by hybridization with biotin-labelled DNA probes specific for the EHEC virulence plasmid, Shiga-like toxin I (SLT-I) or SLT-II. Stool cultures from 6 of 20 cases (30%) and from 2 of 38 controls (5.3%) yielded EHEC (P = 0.0158). EHEC isolates from all HUS cases hybridized with the EHEC plasmid probe and with probes for SLT-I or -II (or both). The serogroups of the isolates included O157, O26, and O111. EHEC causes HUS in Chile, and the biotinylated gene probes are practical diagnostic tools for epidemiologic studies.

Bacterial Toxins↗