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Biomedical subjects

Luis Jimenez

Publications and source records attributed to Luis Jimenez.

8 recordsLinked to original sources

Flavobacteria consume nitrous oxide produced by partial denitrifiers in coastal sediments.

Nearly one-fifth of global emissions of the potent greenhouse gas nitrous oxide (N2O) originate from the ocean, particularly from nutrient-polluted coastal regions. Permeable (sandy) sediments, which cover half of the continental shelf worldwide, are potential sources of N2O due to increasing nutrient inputs from urbanization and agriculture. Yet, the microbial processes determining N2O emissions in these dynamic and unique ecosystems remain understudied. Here, we combined environmental measurements, bacterial cultivation, and genomic analyses to understand the microbes and processes controlling N2O cycling in permeable sediments from Port Phillip Bay (Australia). We established a genomic resource comprising 249 metagenome-assembled genomes and 95 new isolate genomes. Genome-based metabolic reconstructions and culture-based gas measurements revealed that diverse bacteria in these sediments produce N2O through incomplete denitrification pathways. However, these bacteria co-occurred with highly abundant clade II N2O-reducing bacteria from the Flavobacteriaceae family. Kinetic profiling showed that both clade II nosZ flavobacterial isolates and whole sand communities exhibited a low apparent affinity for N2O under the tested experimental conditions, expanding the currently limited kinetic data available for N2O reducing microorganisms from coastal permeable sediments, including flavobacterial clade II N2O reducers. Collectively, these findings indicate that abundant N₂O reducing communities can substantially consume N2O within permeable sediments, thus limiting N2O accumulation despite active N2O production. Together with previous hydrodynamic models predicting low N2O release from permeable sediments, our results highlight the important role of specialized microbial communities in regulating N2O cycling under increasing nutrient pollution.

Nitrous Oxide↗

Virucidal activity of a quaternary ammonium compound disinfectant against feline calicivirus: a surrogate for norovirus.

BACKGROUND: Norovirus, formerly known as Norwalk virus, is an important cause of gastroenteritis outbreaks in hospitals, food services, schools, and cruise ships. Infection control practices by using disinfectants to eliminate noroviruses from surfaces and environmental samples reduce the morbidity and spread of virus outbreaks. There are not many commercial disinfectants effective against norovirus. Noroviruses cannot be cultivated in vitro. However, feline calicivirus can be used as a surrogate to determine disinfectant efficacy against noroviruses. Feline calicivirus was used in a virucidal effectiveness test protocol as a surrogate for norovirus to determine the virucidal efficacy of R-82, a quaternary ammonium compound disinfectant cleaner. METHODS: Feline calicivirus suspensions containing at least 5% fetal bovine serum were dried on carriers and treated with 1:256 dilutions of R-82 disinfectant in water, with a hardness of 400 ppm as calcium carbonate, for 10 minutes. Hypochlorite concentrations of 100 +/- 10 and 1,000 +/- 10 ppm, respectively, were also analyzed as internal control standards. After contact period, the test agents were neutralized with 2 mL of appropriate neutralizer, and mixtures were scraped from carrier surfaces with a cell scraper. Selected dilutions of the neutralized inoculum/test agent mixtures were added to cultured cell monolayers of appropriate host cells. Postincubation, the infectious feline calicivirus was scored microscopically by observing virus-specific cytopathic effects produced by replicating infectious virus. The performance criterion was a minimum of 4-log(10) reduction in cytopathic effects of feline calicivirus. RESULTS: After a 10-minute contact time, formulation R-82 diluted 1:256 showed a 6.6- and 6.4-log(10) reductions in cytopathic effects of feline calicivirus during initial and confirmatory testing, respectively, demonstrating complete inactivation of the virus. A hypochlorite solution of 1,000 ppm exhibited similar log(10) reductions to the quaternary ammonium disinfectant, demonstrating the reproducibility of the protocol. CONCLUSION: Formulation R-82, a quaternary ammonium compound, is a 1-step disinfectant cleaner, which exhibited virucidal activity against feline calicivirus suspensions dried on hard surface carriers. Surfaces are vectors for virus transmission during outbreaks by transferring the virus to people or other environmental surfaces. Therefore, treatment of contaminated surfaces with formulation R-82 will optimize disinfection of noncritical and critical surfaces in health care institutions, reducing the possibility of virus transmission during outbreaks.

Animals↗

Improvement of age-related endothelial dysfunction by simvastatin: effect on NO and COX pathways.

The effects of oral administration of the HMG-CoA reductase inhibitor, simvastatin (SV), on age-related endothelial dysfunction were investigated in the aorta of male Wistar rats. Adult (12-14 weeks) and old (60-80 weeks) rats were treated daily for 12 weeks with either vehicle or SV (1 mg kg(-1)). In old rats, SV treatment did not significantly affect systolic blood pressure and LDL-cholesterol, but it reduced plasma cholesterol, triglycerides and oxidised LDL though it did not affect total antioxidant status. SV improved endothelium-dependent relaxation to acetylcholine and A-23187 in vessels from aged, but not adult, rats. This effect was linked to a greater NO vasodilatation via an increased expression of endothelial NO-synthase. A mechanism sensitive to superoxide dismutase and catalase also accounts for enhanced endothelial vasodilatation. Finally, SV did not affect the release of prostacyclin, but it inhibited the generation of thromboxane (TX) A2 from COX-2 isoform. The effect of the latter was sensitive to the Tp receptor antagonist, ICI-192,605. The present study provides evidence that oral administration of SV improves endothelial dysfunction in the aorta from aged rats by mechanisms associated with enhanced NO vasodilatation, reduced release of TXA2 from cyclo-oxygenase, and increased antioxidant properties of the vessel wall. These data underscore a new therapeutic perspective for SV in age-related endothelial dysfunction.

Acetylcholine↗

Effects of simvastatin on endothelial function after chronic inhibition of nitric oxide synthase by L-NAME.

Blood pressure, plasma NO(2) and NO(3) level, heart weight index, antioxidant enzyme activity, and vascular reactivity in rat intact aortic rings were assessed to investigate the effects of 8-week treatment with the hydroxy-methyl-glutaryl coenzyme A reductase inhibitor simvastatin (1 mg/kg per day) on endothelial dysfunction induced by chronic Nomega-nitro-l-arginine methyl ester (l-NAME 70 mg/kg per day). Results were compared with those obtained in rats receiving l-NAME, simvastatin or control animals. Coadministration of simvastatin did not restore l-NAME-increased blood pressure but normalized heart weight index (P < 0.05), endothelium-dependent relaxation to acetylcholine (P < 0.001), and plasma NO(2) and NO(3) concentration (P < 0.001) without affecting relaxation to sodium nitroprusside. Endothelium-dependent relaxation in these animals was abolished by acute incubation with l-NAME, unaffected by thromboxane synthetase inhibitor and TXA(2)/PGH(2) receptor antagonist, ridogrel, and decreased by indomethacin. Simvastatin treatment also increased plasma NO(2)+NO(3) without affecting endothelial function, heart weight index, and blood pressure of control rats. The presence of superoxide dismutase (SOD) and catalase improved endothelial relaxation only in l-NAME-treated rats, but O(2)- generated by hypoxanthine and xanthine oxidase inhibited the relaxant effect in both l-NAME and simvastatin plus l-NAME-treated rats. SOD activity was increased in all groups receiving simvastatin. Long-term treatment with simvastatin restored l-NAME-induced endothelial dysfunction, probably by preventing nitric oxide decrease. Other effects of simvastatin, including release of compensating vasodilatory cyclo-oxygenase products and increased SOD activity, could also be involved.

Acetylcholine↗

Simvastatin improves endothelial function in spontaneously hypertensive rats through a superoxide dismutase mediated antioxidant effect.

BACKGROUND: Hydroxymethylglutaryl coenzyme A (HMGCoA) reductase inhibitors have beneficial effects beyond their cholesterol-lowering properties. The antioxidant mechanism of HMGCoA reductase inhibitors is not completely understood. OBJECTIVES: To elucidate the antioxidant effect of simvastatin. METHODS: We studied the influence of simvastatin treatment on the development of hypertension, modification of antioxidant systems, and reactivity of aortic rings in Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. RESULTS: Simvastatin had no effect on blood pressure (BP). Simvastatin treatment (either 1 or 2 mg/kg body weight for 12 or 20 weeks) increased superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in SHR rats compared with untreated control SHR rats. Carbachol-induced relaxation of aortic rings was impaired in control SHR rats and was restored by simvastatin treatment. Addition of SOD improved the response in control SHR rats and did not have any effect in treated SHR rats. Addition of diethyldithiocarbamic acid, a selective inhibitor of SOD, produced a mild non-significant impairment in carbachol-induced relaxation in control SHR rats, suggesting a deficient antioxidant system in these animals. However, in treated SHR and in WKY rats, impairment of the relaxation was marked, implying that SOD activity in these animals was important to maintain endothelial function. In aortic rings without endothelium from SHR rats, contraction induced by free radicals was substantially higher than in WKY rats. This effect was attenuated in 1-mg-treated rats and abolished in 2-mg-treated rats. CONCLUSIONS: Simvastatin promotes intracellular antioxidant systems, fundamentally SOD, restoring endothelial function but not having any effect on blood pressure.

Animals↗

Role of ketoconazole treatment in urinary-free cortisol-to-cortisone and tetrahydrocortisol-to-tetrahydrocortisone ratios in nonectopic Cushing's syndrome.

We hypothesized that in nonectopic Cushing syndrome there is an insufficient activity of type II (renal) 11beta-hydroxysteroid dehydrogenase (11beta-HSD2) that is related to cortisol excess, rather than to corticotropin (adrenocorticotropic hormone [ACTH]) levels. We measured plasma ACTH and urinary-free cortisol (UFF), urinary-free cortisone (UFE), tetrahydrocortisol (UTHF), and tetrahydrocortisone (UTHE) in 24-h urine samples of 24 healthy subjects and 15 patients diagnosed with nonectopic Cushing syndrome. Then, in the group of patients, a new 24-h urine sample was collected after treatment with 800 mg daily of ketoconazole. The UFF/UFE and UTHF/UTHE ratios were calculated as an estimation of 11beta-HSD2 activity. The patients had an increase in both the UFF/UFE (19.95 +/- 10.3 vs 5.78 +/- 4.72 nmol/24 h; p < 0.0001) and UTHF/UTHE ratios (5.36 +/- 5.23 vs 1.39 +/- 0.95 nmol/24 h; p < 0.001). Both UFF/UFE and UTHF/UTHE ratios decreased after ketoconazole treatment (19.95 +/- 10.3 vs 12.2 +/- 6.9 nmol/24 h; p < 0.005; and 5.36 +/- 5.23 vs 1.62 vs 1.21 nmol/24 h; p < 0.001, respectively). The control subjects had a significant relationship between UFF and UFE (r = 0.70, p < 0.0001), and between UTHF and UTHE (r = 0.75, p < 0.0001) that did not exist in the patient group. After ketoconazole treatment, the decrease in cortisol excretion in the patient group allowed a positive and significant relation between UFF and UFE (r = 0.64, p < 0.01) and between UTHF and UTHE (r = 0.56, p < 0.05) to appear. There was not any significant relationship between either UFF/UFE or UTHF/UTHE ratios and plasma levels of ACTH.

Adult↗

Adenosine triphosphate bioluminescence analysis for rapid screening of microbial contamination in non-sterile pharmaceutical samples.

An Adenosine Triphosphate (ATP) bioluminescence system was compared and validated against standard methods for rapid microbiological monitoring of several non-sterile pharmaceutical formulations such as creams, tablets, and capsules. Results obtained using 1%, 2.5%, and 10% of product suspensions indicated that most samples that did not contain non-microbial ATP neither inhibited the bioluminescence reaction nor did something else. Ten percent product suspensions were inoculated with different concentrations of Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Salmonella typhimurium, Candida albicans, and Aspergillus niger. Samples were incubated for 24-120 h at 35 degrees C with shaking. Results indicated a strong inhibitory effect of microbial growth, as no microorganisms were detected by using the ATP bioluminescence assay. However, when 1% and 2.5% product suspensions were spiked with the same microorganisms, positive detection was confirmed. After incubation, all microorganisms were detected by the bioluminescence system within 24-72 h. All positive samples were confirmed by using standard plating media. However, to optimize detection of all microorganisms, different enrichment media were developed.

Adenosine Triphosphate↗