Physical and linkage mapping of the porcine pink-eye dilution gene ( OCA2 ).
Explore the source record for details and available documents.
Amino Acid Sequence↗
Biomedical subjects
C Rodríguez
Publications and source records attributed to C Rodríguez.
Factors influencing HIV progression in a seroconverter cohort in Madrid from 1985 to 1999.
OBJECTIVE: To study HIV progression from seroconversion over a 15 year period and measure the population effectiveness of highly active antiretroviral therapy (HAART). METHODS: A cohort study of people with well documented dates of seroconversion. Cumulative risk of AIDS and death were calculated by extended Kaplan-Meier allowing for late entry. Cox proportional hazards models were used to study variables associated with HIV progression. To assess the impact of HAART, calendar time was divided in three periods; before 1992, 1992-6, and 1997-9. RESULTS: From January 1985 to May 2000, 226 seroconverters were identified. The median seroconversion interval was 11 months, median seroconversion date was March 1993. 202 (89%) were men, 76% of whom were homo/bisexual. A 66% reduction in progression to AIDS was observed in 1997-9 compared to 1992-96 (HR 0.34 95% CI: 0.16 to 0.70). People with primary education appeared to have faster progression to AIDS compared to those with university studies (HR 2.69 95%CI: 1.17 to 6.16). An 82% reduction in mortality from HIV seroconversion was observed in 1997-9 (HR 0.18 95% CI: 0.05 to 0.68) compared to 1992-6. Progression to death for people with primary education was twice as fast as for those with university education (p 0.0007). People without confirmation of an HIV negative test had faster progression (HR 4.47 95% CI: 1.18 to 16.92). CONCLUSIONS: The reduction in progression to AIDS and death from seroconversion from 1992-6 to 1997-9 in Madrid is likely to be attributable to HAART. HIV progression was faster in subjects with primary education; better educational level may be associated with better adherence to medication.
Acquired Immunodeficiency Syndrome↗
Pharmacokinetics of marbofloxacin in mature horses after single intravenous and intramuscular administration.
The pharmacokinetic behaviour of marbofloxacin, a new fluoroquinolone antimicrobial agent developed exclusively for veterinary use, was studied in mature horses (n = 5) after single-dose i.v. and i.m. administrations of 2 mg/kg bwt. Drug concentrations in plasma were determined by high performance liquid chromatography (HPLC) and data obtained were subjected to compartmental and noncompartmental kinetic analysis. This compound presents a relatively high volume of distribution (V(SS) = 1.17 +/- 0.18 l/kg), which suggests good tissue penetration, and a total body clearance (Cl) of 0.19 +/- 0.042 l/kgh, which is related to a long elimination half-life (t(1/2beta) = 4.74 +/- 0.8 h and 5.47 +/- 1.33 h i.v. and i.m. respectively). Marbofloxacin was rapidly absorbed after i.m. administration (MAT = 33.8 +/- 14.2 min) and presented high bioavailability (F = 87.9 +/- 6.0%). Pharmacokinetic parameters are not significantly different between both routes of administration (P>0.05). After marbofloxacin i.m. administration, no adverse reactions at the site of injection were observed. Serum CK activity levels 12 h after administration increased over 8-fold (range 3-15) compared with pre-injection levels, but this activity decreased to 3-fold during the 24 h follow-up period. Based on the value of surrogate markers to predict clinical success, Cmax/MIC ratio or AUC/MIC ratio, single daily marbofloxacin dose of 2 mg/kg bwt may not be effective in treating infections in horses caused by pathogens with an MIC > or = 0.25 microg/ml. However, if we use a classical antimicrobial efficacy criteria, marbofloxacin can reach a high plasma peak concentration and maintain concentrations higher than MICs determined for marbofloxacin against most gram-negative veterinary pathogens throughout the administration period. Taking into account the fact that fluoroquinolones are considered to have a concentration-dependent effect and a long postantibiotic effect against gram-negative bacteria, a dose of 2 mg/kg bwt every 24 h could be adequate for marbofloxacin in horses.
Absorption↗
How accurate is preoperative diagnosis by endoscopic biopsies in ampullary tumours?
INTRODUCTION: The benign or malignant nature of ampullary tumours has prognostic and therapeutic implications. On the other hand the difficulty of reaching a correct preoperative diagnosis in these lesions is well known, even when we have a histological study obtained by endoscopic biopsies. MATERIAL AND METHODS: We review all ERCP's in which biopsies of the papilla were taken, performed between January 1991 and September 2000. We analyse the concordance rate between preoperative diagnosis (endoscopic biopsies obtained during ERCP) and definitive diagnosis (surgical specimen) (n = 32), and the possible influence of previous sphincterotomy in our results. RESULTS: In the 32 patients studied global accuracy between pre- and postsurgical diagnosis was 68.7%. This accuracy was markedly higher in the group with ampullary cancer (82.7%) than in the group with ampullary adenoma (50%) (p = 0.12). In the group of patients with sphincterotomy accuracy was 56.25% and increased up to 81.25% in the group of patients without sphincterotomy, although statistical significance was not reached (p = 0.25). CONCLUSIONS: In our series, the accuracy of endoscopic biopsies is higher in the adenocarcinoma group than in the adenoma group, obtaining better results in patients without previous sphincterotomy. The impossibility of a preoperative and absolutely certain confirmation of the benign or malignant nature of ampullary tumours forces us to be cautious in deciding type of surgical resection.
Adenocarcinoma↗
The development of sex differences in the locus coeruleus of the rat.
Development of sex differences in the locus coeruleus (LC) is investigated. The LC is a sexually dimorphic structure in which the female manifests a larger volume and greater number of neurons than do males. Male and female Wistar rats were sacrificed on prenatal days (E) 16 and 20 and postnatally (P) on days 1, 3, 7, 15, 35, 45, 60, and 90. Male and female rats show a continuous increase in the number of neurons after birth that stops in the males by P45 and in females by P60. These findings point out the existence of different patterns of development in male and female rats and may suggest that sex differences could be established because of the existence of a differential period of neurogenesis in both sexes in the postpubertal period.
Aging↗
Time trend in incidence of HIV seroconversion among homosexual men repeatedly tested in Madrid, 1988--2000.
An open cohort of 2670 homosexual men repeatedly tested for HIV at a Madrid clinic has registered 8050 person-years (PY) of follow-up and 157 seroconversions from 1988 to 2000. After declining from 1988 (4.71 per 100 PY), the incidence rate began a significant upward trend, reaching a figure of 2.16 per 100 PY in 2000. These findings ought to alert surveillance systems and prevention programmes.
AIDS Serodiagnosis↗
[Pregnancies in human immunodeficiency virus infection discordant couples].
Explore the source record for details and available documents.
Female↗
[Personality traits and burnout in family doctors].
OBJECTIVE: With this research we try to study personality traits that could be associated with high punctuation at burnout scales (Maslach Burnout Inventory) in primary care physicians. DESIGN: Observational, descriptive, transversal. STUDY SETTING: 93 primary care centres in Barcelona-city and the northern province's region: Vallès Oriental, Vallès Occidental, Maresme, Osona, Bages and Berguedà (centre sanitary region). METHOD: Individual or collective direct interview to 528 primary care physicians. Three questionnaires were administrated: a sociodemographic item one, the Maslach Burnout Inventory (MBI), and the Cattell personality test 16-PF. RESULTS: The 40% of the interviewed physicians had some burnout symptoms without any difference between sexes. 12.4% of these showed very high burnout levels. Those subjects with burnout criteria punctuated different at stability, tension and vigilance traits and anxiety dimension. CONCLUSION: Some personality traits like low stability, the tension and the anxiety are associated with high punctuation of burnout.
Burnout, Professional↗
LDL downregulates CYP51 in porcine vascular endothelial cells and in the arterial wall through a sterol regulatory element binding protein-2-dependent mechanism.
Hypercholesterolemia is associated with endothelial dysfunction and atherosclerotic lesion formation. By mRNA-differential display analysis, we have identified lanosterol 14alpha-demethylase (CYP51) as a gene highly regulated by native LDLs (nLDLs) in endothelial cells. CYP51 is a cytochrome P-450 enzyme involved in the postsqualene phases of cholesterol biosynthesis. CYP51 mRNA levels decrease in nLDL-treated cells in a dose- and time-dependent manner (9-fold after 24 hours with 180 mg of LDL cholesterol per deciliter), an effect that is blocked by cycloheximide. In parallel, sterol regulatory element (SRE) binding protein-2 (SREBP-2) expression falls (10-fold), without alteration in SREBP-1 level. N:-Acetyl-leucyl-leucyl-norleucinal, which inhibits catabolism of the active form of SREBPs, abolished the effect of high concentrations of nLDL on CYP51 expression. Gel-shift assays performed with the SRE of the cyp51 gene (cyp51-SRE) revealed a diminished SREBP-SRE interaction in LDL-treated cells. Moreover, nLDLs downregulate CYP51 promoter activity in transfection assays. Thus, atherogenic levels of nLDL downregulate endothelial CYP51 mRNA levels through a reduction in SRE-SREBP-2 interaction. Additionally, SREBP-2 and CYP51 mRNA levels are decreased in the arterial wall of hypercholesterolemic pigs. In summary, we have described for the first time, both in in vivo and in vitro systems, that CYP51 is expressed in the vascular wall and that it is downregulated together with SREBP-2 by high levels of nLDL. Because this transcription factor controls multiple cell lipid metabolism pathways, its regulation by nLDL could play a key role in lipid-mediated endothelial dysfunction.
Animals↗
Differential induction of stearoyl-CoA desaturase and acyl-CoA oxidase genes by fibrates in HepG2 cells.
We studied whether two typical effects of fibrates, induction of stearoyl-CoA desaturase (EC 1.14.99.5) and peroxisome proliferation, are related. The effect of bezafibrate on the activity and mRNA of stearoyl-CoA desaturase and acyl-CoA oxidase in the liver and epididymal white adipose tissue of male Sprague-Dawley rats was determined. The same parameters were measured in HepG2 cells, a cell line resistant to peroxisome proliferation, following incubation with ciprofibrate. Bezafibrate increased the hepatic mRNA levels (14.5-fold on day 7) and activity (9.3-fold on day 15) of acyl-CoA oxidase. Stearoyl-CoA desaturase mRNA levels were transiently increased (2.7-fold on day 7), while its activity remained increased at the end of the treatment (2.4-fold). In white adipose tissue, bezafibrate increased the mRNA (5-fold) and activity (1.9-fold) of acyl-CoA oxidase, while stearoyl-CoA desaturase was not modified. Ciprofibrate addition to HepG2 cells cultured in 7% fetal bovine serum (FBS) only increased the stearoyl-CoA desaturase mRNA (1.9-fold). When cells were cultured in 0.5% FBS, ciprofibrate increased acyl-CoA oxidase mRNA (2.2-fold), while the increase in stearoyl-CoA desaturase mRNA was identical (1.9-fold). Further, its activity was also increased (1.5-fold). Incubation of HepG2 cells in the presence of cycloheximide did not alter the capacity of ciprofibrate to induce stearoyl-CoA desaturase mRNA, whereas the presence of actinomycin abolished the induction. In addition, preincubation of HepG2 cells with ciprofibrate increased the rate of stearoyl-CoA desaturase mRNA degradation. The results presented in this study suggest that fibrates induce stearoyl-CoA desaturase activity and mRNA levels independently of peroxisome proliferation.
Acyl-CoA Oxidase↗
Primary genotypic and phenotypic HIV-1 drug resistance in recent seroconverters in Madrid.
OBJECTIVE: Transmission of drug-resistant HIV-1 strains is increasing with widespread use of antiretroviral drugs in developed countries. This study examined the prevalence of resistant viruses in recent seroconverters in Madrid, Spain. DESIGN: HIV isolates from 30 consecutive participants with positive or indeterminate HIV antibody test results and a negative test result at a mean of 6.6 months earlier were examined for HIV drug resistance. All study subjects admitted to having very recently engaged in high-risk practices. All were therapeutically naive and were recruited between 1997 and 1999 in a referring health care facility for sexually transmitted diseases. METHODS: Population-based sequencing of the viral reverse transcriptase (RT) and protease (PR) regions derived from plasma viral RNA was performed. Phenotypic resistance was assessed by a recombinant virus assay. RESULTS: Overall prevalence of genotypes associated with reduced susceptibility was 26.7% (8 of 30 participants). Resistance mutations were seen against nucleoside analogues in 7 (23.3%), nonnucleoside reverse transcriptase inhibitors in 1 (3.3%), and protease inhibitors in 2 (6.7%). Zidovudine-resistance mutations M41L and/or T215Y were the commonest, found in 20% (6 of 30 participants). Resistance mutations to at least two antiretroviral families (multidrug-resistance) were detected in 2 (6.7%) study subjects. A median infectious dose (IC50) increase of fourfold for any drug was found in 7 patients, and in 2 was > tenfold for zidovudine (genotype M41L + T215Y) and lamivudine (genotype M184V), respectively. CONCLUSIONS: Drug-resistant HIV variants were present in over one quarter of individuals recently diagnosed as infected in Madrid, Spain. Therefore, resistance testing at baseline should be considered for the optimal design of first-line antiretroviral combinations.
Drug Resistance, Microbial↗
Bezafibrate induces acyl-CoA oxidase mRNA levels and fatty acid peroxisomal beta-oxidation in rat white adipose tissue.
Rats treated with bezafibrate, a PPAR activator, gain less body weight and increase daily food intake. Previously, we have related these changes to a shift of thermogenesis from brown adipose tissue to white adipose tissue attributable to bezafibrate, which induces uncoupling proteins (UCP), UCP-1 and UCP-3, in rat white adipocytes. Nevertheless, UCP induction was weak, implying additional mechanisms in the change of energy homeostasis produced by bezafibrate. Here we show that bezafibrate, in addition to inducing UCPs, modifies energy homeostasis by directly inducing aco gene expression and peroxisomal fatty acid beta-oxidation in white adipose tissue. Further, bezafibrate significantly reduced plasma triglyceride and leptin concentrations, without modifying the levels of PPARgamma or ob gene in white adipose tissue. These results indicate that bezafibrate reduces the amount of fatty acids available for triglyceride synthesis in white adipose tissue.
Acyl-CoA Oxidase↗
The disposition of marbofloxacin in Eurasian buzzards (Buteo buteo) after intravenous administration.
Explore the source record for details and available documents.
Animals↗
Influence of ruminal distribution on norfloxacin pharmacokinetics in adult sheep.
Norfloxacin (NF) ruminal distribution after intravenous (i.v.), intramuscular (i.m.) and oral (p.o.) administration was determined in order to assess the influence of the rumen on the pharmacokinetic behaviour of NF in sheep. Norfloxacin concentrations in rumen were detected after i.v. and i.m. administrations between 4 and 48 h in all animals studied. The experimental distribution ratios after i.v. and i.m. administration expressed as area under the concentration-time curve ratios AUC(rumen)/AUC(plasma) were 0.24 and 0.39, respectively, and thus lower than corresponding predicted value of 5.06. Apparently, drug persisted in the rumen content longer than in plasma. The experimental mean residence time ratios MRT(rumen)/MRT(plasma) after i.v. and i.m. administrations were 2.33 and 1.66, respectively. After p.o. administration, NF concentrations in the rumen content were extremely high compared with the respective plasma concentrations, resulting in mean peak concentrations ratio C(max-rumen)/C(max-plasma) of 383.66 and AUC(rumen)/AUC(plasma) experimental ratio of 402.32. This value was considerably higher (approximately 79 fold) than the predicted distribution ratio of 5.06. Our results suggest that the limited p.o. bioavailability of NF in ruminants could not be attributed to ruminal degradation.
Administration, Oral↗
Pharmacokinetic behavior of marbofloxacin after intravenous and intramuscular administrations in adult goats.
The pharmacokinetic behavior of marbofloxacin was studied in goats after single-dose intravenous (i.v.) and intramuscular (i.m.) administrations of 2 mg/kg bodyweight. Drug concentration in plasma was determined by high performance liquid chromatography (HPLC) and the data collected were subjected to compartmental and noncompartmental kinetic analysis. This compound presented a relatively high volume of distribution (Vss=1.31 L/kg), which suggests good tissue penetration, and a total body clearance (Cl) of 0.23 L/kg small middle doth, which is related to a long elimination half-life (t1/2beta=7.18 h and 6.70 h i.v. and i.m., respectively). Pharmacokinetic parameters were not significantly different between both routes of administration. Marbofloxacin was rapidly absorbed after i.m. administration (Tmax=0.9 h) and had high bioavailability (F=100.74%).
Animals↗
Chiral pharmacokinetics of ketorolac in sheep after intravenous and intramuscular administration of the racemate.
Explore the source record for details and available documents.
Animals↗
Pharmacokinetic behaviour of phenylglyoxal bis(guanylhydrazone) (PGBG) after intravenous administration in rabbits.
Phenylglyoxal bis(guanylhydrazone) (PGBG) is a synthesized analogue of methylglyoxal bis(guanylhydrazone) (MGBG), which has demonstrated anti-parasitic activity in rabbits. The pharmacokinetic behaviour of PGBG after intravenous administration (10 mg/kg bodyweight) was studied in five rabbits. Plasma concentrations of PGBG were measured by high-performance liquid chromatography. Plasma PGBG concentrations decreased rapidly and were not detectable beyond 90 min after treatment. The mean [+/- standard deviation (SD)] volume of distribution at steady state (Vdss) was 2.19 +/- 0.47 l/kg and the mean plasma clearance value (Cl) was 29.99 +/- 3.98 ml/min kg. This drug is rapidly eliminated from the body in rabbits, having a short elimination half-life (0.93 h) and mean residence time (1.21 h).
Animals↗
Randomized comparison of long-term losartan versus propranolol in lowering portal pressure in cirrhosis.
BACKGROUND & AIMS: It has been suggested that losartan, an angiotensin II (A-II) type 1 receptor blocker, may have a pronounced portal pressure reducing effect, far greater than that of propranolol. This randomized controlled trial compared the hemodynamic and renal effects of continued 6-week administration of losartan (n = 25) vs. propranolol (n = 15) in portal hypertensive patients with cirrhosis treated endoscopically after a variceal bleeding episode. METHODS: Hepatic venous pressure gradient (HVPG), systemic hemodynamics, renal function, and vasoactive factors were measured before and at 6 weeks of treatment. RESULTS: Losartan did not reduce HVPG (-2% +/- 12%, NS) but significantly decreased mean arterial pressure (MAP, -8% +/- 10%, P = 0.001). On the contrary, propranolol significantly reduced HVPG (-10% +/- 11%, P = 0.003) and cardiac output (-16% +/- 12%, P = 0.001) but did not modify MAP (2.5% +/- 10%, NS). Losartan increased A-II levels, reduced aldosterone, and decreased glomerular filtration rate (GFR) in Child B patients. Propranolol did not modify renal function. Adverse events related to therapy were mild and similar in both groups. CONCLUSIONS: Unlike propranolol, long-term losartan administration does not significantly reduce HVPG in patients with cirrhosis treated after a variceal bleeding episode, and it caused hypotension and reduced GFR in patients with moderate liver failure. Therefore, losartan is not an alternative to propranolol in preventing variceal rebleeding.
Adult↗