Effect assessment of antimicrobial pharmaceuticals on the aquatic plant Lemna minor.
Explore the source record for details and available documents.
Anti-Bacterial Agents↗
Biomedical subjects
J A Ortiz
Publications and source records attributed to J A Ortiz.
Prevalence of erectile dysfunction in Colombia, Ecuador, and Venezuela: a population-based study (DENSA).
The purpose of this study was to estimate the prevalence of erectile dysfunction (ED) in Colombia, Ecuador, and Venezuela. A 49-item questionnaire was completed by 1946 men aged 40 years and older. The age-adjusted combined prevalence of minimal, moderate, and complete ED for all three countries was 53.4%, with 19.8% of all men reporting moderate to complete ED. Age was the variable most strongly linked to ED; the prevalence of complete ED increased markedly in men older than 79 y of age (31.9%) and 70-79 y (17.2%) compared with men aged 40-49 y (<3%). Several medical conditions, such as hypertension, benign prostatic hyperplasia, and diabetes, and the use of medications to treat these conditions were correlated with the prevalence of ED. This study corroborates earlier studies demonstrating that ED is very common, increases dramatically with age, and has multiple correlates, including some that are also risk factors for cardiovascular disease.
Adult↗
Conserved interaction between distinct Krüppel-associated box domains and the transcriptional intermediary factor 1 beta.
The Krüppel-associated box (KRAB) domain, originally identified as a 75-aa sequence present in numerous Krüppel-type zinc-finger proteins, is a potent DNA-binding-dependent transcriptional repression domain that is believed to function through interaction with the transcriptional intermediary factor 1 (TIF1) beta. On the basis of sequence comparison and phylogenetic analysis, we have recently defined three distinct subfamilies of KRAB domains. In the present study, individual members of each subfamily were tested for transcriptional repression and interaction with TIF1 beta and two other closely related family members (TIF1 alpha and TIF1 gamma). All KRAB variants were shown, (i) to repress transcription when targeted to DNA through fusion to a heterologous DNA-binding domain in mammalian cells, and (ii) to interact specifically with TIF1 beta, but not with TIF1 alpha or TIF1 gamma. Taken together, these results implicate TIF1 beta as a common transcriptional corepressor for the three distinct subfamilies of KRAB zinc-finger proteins and suggest a high degree of conservation in the molecular mechanism underlying their transcriptional repression activity.
Animals↗
Low activity of mitochondrial HMG-CoA synthase in liver of starved piglets is due to low levels of protein despite high mRNA levels.
The unusually low hepatic ketogenic capacity of piglets has been correlated with lack of expression of the mitochondrial HMG-CoA synthase gene. However, we have shown that starvation of 2-week-old piglets increased the mRNA levels of mitochondrial HMG-CoA synthase to a level similar to that observed in starved rats (S. H. Adams, C. S. Alho, G. Asins, F. G. Hegardt, and P. F. Marrero, 1997, Biochem. J. 324, 65-73). We now report that antibodies against pig mitochondrial HMG-CoA synthase detected the pig enzyme in mitochondria of 2-week-old starved piglets and that the pig mitochondrial HMG-CoA synthase cDNA encodes an active enzyme in the eukaryotic cell line Mev-1, with catalytic behavior similar to that of the rat enzyme when expressed in the same system. We also show that low activity of pig mitochondrial HMG-CoA synthase correlates with low expression of the pig enzyme. The discrepancy in mitochondrial HMG-CoA synthase gene expression between the high levels of mRNA and low levels of enzyme was not associated with differences in transcript maturation, which suggests that an attenuated translation of the pig mRNA is responsible for the diminished ketogenic capacity of pig mitochondria.
Animals↗
Is intraoperative cholangiography during laparoscopic cholecystectomy cost effective?
BACKGROUND: Common bile duct injuries occur in 0.2% to 0.8% of laparoscopic cholecystectomies (LC). Intraoperative cholangiograms (IOCG) are a useful means of detecting common bile duct injuries in the operating room. METHODS: Data were retrospectively reviewed for patients referred for management of common duct injuries from 1996 to 2000. Cost data were obtained from hospital records. Legal settlements were obtained from published sources. RESULTS: Twenty-one patients (0.133%) were found to have bile duct injuries and incurred median hospital stays of 11.5 days at an average cost of $587,491. The average cost of those requiring reoperation was $669,134. The 21 cases in our sample had total charges of $10,819,767. Performing IOCG during each LC in Orange County would have cost $10,669,725. If extrapolated to state and nationwide levels, the savings is far greater. CONCLUSIONS: IOCG during LC is a cost-effective means of preventing the costs of delayed recognition of bile duct injuries.
Adult↗
Heterochromatin formation in mammalian cells: interaction between histones and HP1 proteins.
Members of the heterochromatin protein 1 (HP1) family are silencing nonhistone proteins. Here, we show that in P19 embryonal carcinoma (EC) nuclei, HP1 alpha, beta, and gamma form homo- and heteromers associated with nucleosomal core histones. In vitro, all three HP1s bind to tailed and tailless nucleosomes and specifically interact with the histone-fold of histone H3. Furthermore, HP1alpha interacts with the linker histone H1. HP1alpha binds to H3 and H1 through its chromodomain (CD) and hinge region, respectively. Interestingly, the Polycomb (Pc1/M33) CD also interacts with H3, and HP1alpha and Pc1/M33 binding to H3 is severely impaired by CD mutations known to abrogate HP1 and Polycomb silencing in Drosophila. These results define a novel function for the conserved CD and suggest that HP1 self-association and histone binding may play a crucial role in HP1-mediated heterochromatin assembly.
Amino Acid Sequence↗
Bonus, a Drosophila homolog of TIF1 proteins, interacts with nuclear receptors and can inhibit betaFTZ-F1-dependent transcription.
The Drosophila bonus (bon) gene encodes a homolog of the vertebrate TIF1 transcriptional cofactors. bon is required for male viability, molting, and numerous events in metamorphosis including leg elongation, bristle development, and pigmentation. Most of these processes are associated with genes that have been implicated in the ecdysone pathway, a nuclear hormone receptor pathway required throughout Drosophila development. Bon is associated with sites on the polytene chromosomes and can interact with numerous Drosophila nuclear receptor proteins. Bon binds via an LxxLL motif to the AF-2 activation domain present in the ligand binding domain of betaFTZ-F1 and behaves as a transcriptional inhibitor in vivo.
Amino Acid Motifs↗
Laparoscopic ultrasound with radiofrequency ablation in cirrhotic patients with hepatocellular carcinoma: technique and technical considerations.
The optimal treatment for hepatocellular carcinoma (HCC) is surgical resection. However, only a small percentage of patients are operative candidates. CT-guided percutaneous radiofrequency ablation (RFA) has been shown to be efficacious in treatment of unresectable HCC. CT-guided RFA, however, may fail to detect small intrahepatic metastases and tumor thrombi, which thus minimizes possible gains from the procedure. Recent advances in laparoscopic ultrasound have greatly improved the accuracy in detecting intrahepatic HCC metastases many of which were missed by CT. Combining intraoperative laparoscopic ultrasound with laparoscopic RFA greatly utilizes advances in both fields and is technically feasible. Our objective is to introduce a novel operative combination of laparoscopic ultrasound with laparoscopic RFA in treatment of HCC. Childs class B patients with unresectable HCC were considered for this study. Twelve patients underwent laparoscopic ultrasound and RFA of 17 lesions. Tumors ranged from 0.27 to 7 cm in diameter. Laparoscopic ultrasound identified tumor not detected preoperatively in one patient (8.3%). A single pneumothorax was the only complication. A single patient (8.3%) had recurrent disease and accounted for the only mortality in the study. We conclude that the use of both laparoscopic ultrasound and RFA is an excellent use of existing technology. The procedure combines improved tumor localization with the means to treat patients with unresectable disease. Because RFA is a relatively recent development long-term results are not yet available. Randomized prospective studies comparing RFA with other modalities will determine the ultimate utility of this procedure.
Adult↗
A system dynamic model for the assessment of different exposure routes in aquatic ecosystems.
With the exception of a limited number of highly persistent lipophilic pollutants, waterborne exposure is considered the most relevant exposure route for aquatic organisms, and even the only relevant exposure route in lower tier assessment, while the potential for bioaccumulation is only evaluated as secondary poisoning for birds and mammals. In addition, some evaluations consider that only the dissolved fraction is bioavailable for pelagic organisms. The lack of easy and cost-effective assessment methods is probably the main reason to disregard the contribution of other routes. This paper presents a system dynamics model that estimates the time-dependent accumulation of toxic chemicals through the food chain, and has also the potential to include the exposure from sediment. The generic ecosystem includes a primary producer and three levels of consumers, represented by unicellular algae, cladoceran invertebrates, cladoceran-eating fish and fish-eating fish, respectively. Nevertheless, the model, built using Microsoft Excel software, allows any number of levels and ecological-exposure relationships. The results obtained for four illustrative pollutants demonstrate that factors such as the binding to algae and other edible particles or food chain exposure for lipophilic non-persistent chemicals may constitute significant exposure routes. The current low tier European ecological risk assessment guidelines do not cover these aspects, and therefore may under estimate the real risk for both aquatic organisms and their predators. The model includes a simplified worst-case alternative that normally can be calculated using the existing information. Under a tiered approach, the simplified alternative is proposed to trigger the need of the toxicokinetics assays required to perform the complete time-dependent calculation.
Animals↗
Sterol regulatory element binding protein-mediated effect of fluvastatin on cytosolic 3-hydroxy-3-methylglutaryl-coenzyme A synthase transcription.
The effects of acute treatment with fluvastatin, a hypocholesteremic drug, on the mRNA levels of several regulatory enzymes of cholesterogenesis and of the LDL receptor were determined in rat liver. Fluvastatin increased the hepatic mRNA levels for HMG-CoA reductase up to 12-fold in 5 weeks of treatment at a daily dose of 6. 3 mg/kg. The effect was less marked in cytosolic HMG-CoA synthase, farnesyl-PP synthase, squalene synthetase, and LDL receptor. SREBP-2 mRNA levels were also increased, but SREBP-1 were not. De novo synthesis of cholesterol in several cultured cells was reduced by increasing concentrations of fluvastatin, and the IC(50) values of fluvastatin in HepG2, CV-1, and CHO cells were respectively 0.01, 0. 05, and 0.1 microM. When CHO cells stably transfected with a chimeric gene composed of the promoter of cytosolic HMG-CoA synthase and the CAT gene as a reporter were incubated with fluvastatin, the CAT gene was overexpressed, an effect which was similar to the cotransfection with the processed form of SREBP-1a. Both ALLN and fluvastatin increased the transcriptional activity of cytosolic HMG-CoA synthase. Mutation in either SRE or NF-Y boxes abolished the increase in transcriptional rate caused by fluvastatin in the promoter of cytosolic HMG-CoA synthase. These results indicate that the increase in transcriptional activity in the HMG-CoA synthase gene attributable to fluvastatin is a consequence of the activation of the proteolytic cleavage of SREBPs by reduced levels of intracellular cholesterol.
Animals↗
Sertaconazole: pharmacology of a gynecological antifungal agent.
Sertaconazole is a broad spectrum antifungal agent with excellent activity against yeasts, dermatophytes and opportunistic fungi. In addition to this antifungal efficacy, it has a good safety profile, sustained cutaneous retention, and low systemic absorption, all of which make it ideal for topical applications. In this study, the pharmacological properties of sertaconazole related to the treatment of vaginal fungi, in particular vulvovaginal candidiasis, are reviewed. As with all other infectious processes, the interacting components are infectious microorganism, host and drug. The following properties of sertaconazole have been investigated in pre-clinical studies: its in vitro spectrum of activity and potency against causative agents and accompanying factors in vaginal infection; its mechanism of action, whether it acts on the pathogenic properties of the microorganism; if it affects host defense mechanisms and how its antifungal activity is manifested in vivo in experimental candidiasis in the mouse.
Antifungal Agents↗
Complication rates associated with different treatments for mandibular fractures.
PURPOSE: This study compared the complication rate with different types of mandibular fracture treatment (maxillomandibular fixation, 2-mm miniplates, 2.4-mm AO plates, and 2.7-mm AO plates). PATIENTS AND METHODS: A total of 245 patients who presented with 386 fractures were retrospectively analyzed. Patient characteristics, type of fracture, severity of fracture, type of treatment used, and occurrence of complications were recorded. Statistical analysis was used to compare complication rates, fracture severity, and type of treatment. RESULTS: There were no differences in the complication rates for the different types of treatment. There was a significant correlation (P < .05) between fracture severity and the overall complication rate, postoperative infection, and postoperative malocclusion, but there was no significant correlation between these complications and the type of treatment applied. CONCLUSION: The occurrence of postoperative complications in the treatment of mandibular fractures is fundamentally related to the severity of the fracture rather than to the type of treatment used.
Adolescent↗
Cytidine (5')diphosphocholine modulates dopamine K(+)-evoked release in striatum measured by microdialysis.
Experiments were performed to determine whether exogenous cytidine (5')diphosphocholine (CDP-choline) could modify the release of dopamine (DA) in the striatum. Rats were divided into two groups, receiving either a standard diet (UAR 004) or the same diet supplemented with CDP-choline (250 mg/kg day) for 28 days. On the last day the dialysis probes were inserted in the striatum, and DA, homovanillic acid (HVA), and 3,4-dihydroxyphenylacetic acid (DOPAC) efflux were measured in the dialysis stream basally and during K+ depolarization (80 mM K+). Basal DA, HVA, and DOPAC did not show any difference between treated and untreated groups. Depolarization with K+ increased DA levels by up to 3,000% in the control group and by up to 4,770% in the CDP-choline-treated group (p < 0.05), and reduced extracellular HVA and DOPAC concentration by up to 45 and 35%, respectively, both in the untreated and CDP-choline-treated groups. These results show that long-term treatment with CDP-choline increases the K+ induced release DN and suggest, in accordance with previous research, that by providing exogenous choline and cytidine, CDP-choline modulates dopaminergic transmission.
3,4-Dihydroxyphenylacetic Acid↗
Interaction with members of the heterochromatin protein 1 (HP1) family and histone deacetylation are differentially involved in transcriptional silencing by members of the TIF1 family.
Mammalian TIF1alpha and TIF1beta (KAP-1/KRIP-1) are related transcriptional intermediary factors that possess intrinsic silencing activity. TIF1alpha is believed to be a euchromatic target for liganded nuclear receptors, while TIF1beta may serve as a co-repressor for the large family of KRAB domain-containing zinc finger proteins. Here, we report an association of TIF1beta with both heterochromatin and euchromatin in interphase nuclei. Co-immunoprecipitation of nuclear extracts shows that endogenous TIF1beta, but not TIF1alpha, is associated with members of the heterochromatin protein 1 (HP1) family. However, in vitro, both TIF1alpha and TIF1beta interact with and phosphorylate the HP1 proteins. This interaction involves a conserved amino acid motif, which is critical for the silencing activity of TIF1beta but not TIF1alpha. We further show that trichostatin A, an inhibitor of histone deacetylases, can interfere with both TIF1 and HP1 silencing. The silencing activity of TIF1alpha appears to result chiefly from histone deacetylation, whereas that of TIF1beta may be mediated via both HP1 binding and histone deacetylation.
Amino Acid Sequence↗
Isolation of pig mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase gene promoter: characterization of a peroxisome proliferator-responsive element.
Low expression of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase gene during development correlates with an unusually low hepatic ketogenic capacity and lack of hyperketonaemia in piglets. Here we report the isolation and characterization of the 5' end of the pig mitochondrial HMG-CoA synthase gene. The 581 bp region proximal to the transcription start site permits transcription of a reporter gene, confirming the function of the promoter. The pig mitochondrial HMG-CoA synthase promoter is trans-activated by the peroxisomal proliferator-activated receptor (PPAR), and a functional response element for PPAR (PPRE) has been localized in the promoter region. Pig PPRE is constituted by an imperfect direct repeat (DR-1) and a downstream sequence, both of which are needed to confer PPAR-sensitivity to a thymidine kinase promoter and to form complexes with PPAR.retinoid X receptor heterodimers. A role of PPAR trans-activation in starvation-associated induction of gene expression is suggested.
Amino Acid Sequence↗
Characterization of a response element for peroxisomal proliferator activated receptor (PPRE) in human muscle-type carnitine palmitoyltransferase I.
Explore the source record for details and available documents.
Animals↗
Comparative in vitro and in vivo inhibition of cytochrome P450 CYP1A2, CYP2D6, and CYP3A by H2-receptor antagonists.
The isozymes CYP1A2, CYP2D6, and CYP3A4/5 are involved in the majority of all cytochrome P450-mediated drug biotransformations. In this study we investigated the inhibition profiles of CYP1A2 (substrate: caffeine) CYP2D6 (substrate: dextromethorphan), and CYP3A4/5 (substrate: dextrorphan) by cimetidine, ranitidine, and the novel H2-receptor antagonist ebrotidine in human liver microsomes. The inhibitory effect of the drugs on the enzymes activities were as follows: CYP1A2: cimetidine >> ranitidine = ebrotidine; CYP2D6: cimetidine >>> ranitidine = ebrotidine; CYP3A4/5: ebrotidine > cimetidine >>> ranitidine. The inhibition of CYP3A4/5 enzyme activity by ebrotidine was competitive. To test whether the inhibitory effect of ebrotidine in CYP3A activity was also found in vivo, we analyzed the biodisposition of midazolam in 8 healthy volunteers. Midazolam biodisposition was significantly reduced when administered together with cimetidine (P < .05), whereas no significant inhibition was observed with ebrotidine or ranitidine compared with placebo. Psychomotor performance analysis revealed no significant effect of the observed reduction on midazolam biodisposition. We concluded that patients who are receiving treatment with drugs metabolized through CYP3A may experience enhanced drug effects as a result of pharmacokinetic interaction when treated concomitantly with cimetidine. In contrast, the effect of ranitidine or ebrotidine on CYP3A activity in vivo seems to have little clinical significance.
Adult↗
7-[3-(1-piperidinyl)propoxy]chromenones as potential atypical antipsychotics. 2. Pharmacological profile of 7-[3-[4-(6-fluoro-1, 2-benzisoxazol-3-yl)-piperidin-1-yl]propoxy]-3-(hydroxymeth yl)chromen -4-one (abaperidone, FI-8602).
A series of novel 7-[3-(1-piperidinyl)propoxy]chromenones was synthesized and tested as potential antipsychotics in several in vitro and in vivo assays. The compounds possessed good affinity for D2 receptors, together with a greater affinity for 5-HT2 receptors, a profile which has been proposed as a model for atypical antipsychotics. Several agents also displayed a high potency in the climbing mice assay on oral administration, suggesting a potent antipsychotic effect as compared to reference standards. Compound 23 was selected for further pharmacological evaluation. Induction of catalepsy and inhibition of stereotypies weaker than standards, along with a lower increase in serum prolactin levels, were indicative of a potential atypical profile for this compound. From these results, 7-[3-[4-(6-fluoro-1, 2-benzisoxazol-3-yl)piperidin-1-yl]propoxy]-3-(hydroxymethyl )chromen- 4-one (23, abaperidone) has been proposed for clinical evaluation in humans as a potential atypical antipsychotic.
Administration, Oral↗