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Biomedical subjects

M Valle

Publications and source records attributed to M Valle.

At least 55 records · Page 3Linked to original sources
PubMed2000

Modeling of the in vivo antinociceptive interaction between an opioid agonist, (+)-O-desmethyltramadol, and a monoamine reuptake inhibitor, (-)-O-desmethyltramadol, in rats.

The pharmacokinetic-pharmacodynamic (pk-pd) characterization of the in vivo antinociceptive interaction between (+)-O-desmethyltramadol [(+)-M1] and (-)-O-desmethyltramadol [(-)-M1], main metabolites of tramadol, was studied in three groups of rats. (+)-M1 and (-)-M1, both with different pd properties, were studied under steady-state and nonsteady-state conditions, depending on the group. Plasma drug concentration and antinociception were simultaneously measured in each animal by using an enantioselective analytical assay and the tail-flick test, respectively. Respiratory depression also was evaluated in another series of experiments according to the same experimental conditions. The pk behavior was similar for both enantiomers and no significant (P >.05) interaction between two compounds was found at this level. However, a significant (P <.01) potentiation in the antinociceptive effect elicited by (+)-M1 was found during and after (-)-M1 administration. The pd model used to describe the time course of the antinociception in the presence of (+)-M1, (-)-M1, or both is based on previous knowledge of the compounds and includes the following: 1) an effect compartment model to account for the opioid effect of (+)-M1, and 2) an indirect response model accounting for the release of noradrenaline (NA) caused by (+)-M1, and the inhibition of the NA reuptake due to the action of (-)-M1. The model predicts a positive contribution to antinociception of the predicted increasing levels of NA. No significant (P >.05) respiratory effects were seen during or after (+)-M1 and (-)-M1 administration.

Analgesics, Opioid↗
PubMed2000

[Ultrasonography features of the diaphragmatic crura: normal anatomy and its variants].

PURPOSE: To report the various US patterns of the diaphragmatic crura and the changes occurring during the different phases of respirations. The diaphragm has two US patterns: the central membranous part appears highly reflective while the posterior, upper and lateral muscular portions are hypoechoic and thick. The crura can sometimes appear quite bulky, which appearance is easy to misinterpret. MATERIAL AND METHODS: We carried out a three-stage work: first we reviewed the US examinations of 23 subjects with a nodular appearance of the posteromedial bundles and studied the changes in thickness during respiration. Second we studied the diaphragmatic crura in 30 subjects aged 18-71 years, 15 men and 15 women. We used a commercially available unit with sector and convex 3.5 MHz probes at baseline and during breath hold and acquired multiple parasagittal and transverse scans. The crura thickness was measured in all patients. Last, we studied the diaphragmatic regions of 10 patients with right pleural effusion and of 8 patients with associated ascites and pleural effusion using 2.0-5.0 MHz convex phased-array transducers. RESULTS: We found focal thickening of the crura in 11 of 23 patients with US findings of diaphragmatic nodules, but only in deep inspiration. The thickening was 1.5-2.2 cm long and maximum thickness was 10 mm. In the other 12 subjects we found 9 small lobules in the right and 3 in the left crus. In the anatomic study, we observed a 3-band appearance of the diaphragmatic crura, probably referable to muscle bundles, in 30 subjects on sagittal images, in 12 on coronal images and in 28 on anterior transverse images. The diaphragmatic crura were identified in 26 subjects only. The left posterior crus was identified in 29 subjects on left coronal images and in 15 on anterior transverse images; it was demonstrated on anterior sagittal images in close proximity to the aorta in only 4 subjects. Right crus thickness, measured on sagittal scans, ranged 3-10 mm in deep inspiration and 1-4 mm in expiration while the left crus was 3-6 mm in inspiration and 1-2 mm in expiration. The length of the right crus, studied in the preaortic portion, ranged from 7 cm in deep inspiration to 9.7 cm in expiration while the left one was 6.5 to 8.8 cm. The right lateral diaphragmatic bundles were seen in 28 subjects only on repeated subcostal oblique scans and the the left ones in 11 subjects only. Finally the thin anterior bundles were shown on parasagittal images in 13 cases in the right side and in 2 in the left. A 2-band appearance of the diaphragm was seen in 10 patients with pleural effusion and in 8 patients with associated ascites. A single band was found only in the tendinous portion of the diaphragm. DISCUSSION AND CONCLUSIONS: US is presently considered the imaging method of choice in the assessment of changes in thickness and length of the diaphragmatic crura. These structures have different US patterns and can sometimes appear quite bulky and thus be easily mistaken for other anatomic or abnormal structures; orthogonal scans may be required for the differential diagnosis.

Adolescent↗
PubMed1999

Characterization of ATP and DNA binding activities of TrwB, the coupling protein essential in plasmid R388 conjugation.

TrwB is the conjugative coupling protein of plasmid R388. TrwBDeltaN70 contains the soluble domain of TrwB. It was constructed by deletion of trwB sequences containing TrwB N-proximal transmembrane segments. Purified TrwBDeltaN70 protein bound tightly the fluorescent ATP analogue TNP-ATP (K(s) = 8.7 microM) but did not show measurable ATPase or GTPase activity. A single ATP binding site was found per TrwB monomer. An intact ATP-binding site was essential for R388 conjugation, since a TrwB mutant with a single amino acid alteration in the ATP-binding signature (K136T) was transfer-deficient. TrwBDeltaN70 also bound DNA nonspecifically. DNA binding enhanced TrwC nic cleavage, providing the first evidence that directly links TrwB with conjugative DNA processing. Since DNA bound by TrwBDeltaN70 also showed increased negative superhelicity (as shown by increased sensitivity to topoisomerase I), nic cleavage enhancement was assumed to be a consequence of the increased single-stranded nature of DNA around nic. The mutant protein TrwB(K136T)DeltaN70 was indistinguishable from TrwBDeltaN70 with respect to the above properties, indicating that TrwB ATP binding activity is not required for them. The reported properties of TrwB suggest potential functions for conjugative coupling proteins, both as triggers of conjugative DNA processing and as motors in the transport process.

Adenosine Triphosphate↗
PubMed1999

Domain architecture of the bacteriophage phi29 connector protein.

Viral connectors are essential components of the DNA packaging machinery. They interact with nucleic acids and other viral components to translocate DNA inside the viral head. We have attempted to locate the different structural and functional domains of the phage Phi29 connector using a combination of approaches to generate different antigenic probes. Complexes of native connectors with either monoclonal or monospecific antibodies were studied by immunoelectron microscopy and image averaging methods. The data were merged in a model of the connector domain structure at 2-3 nm resolution. This epitope mapping provides a general outline of the folding architecture of the connector polypeptide, following a complicated threading that places the amino and carboxyl-terminals in close alignment in the narrower domain at 2-3 nm from the top of the connector. The appendages are built up by a long and highly immunogenic sequence (amino acid residues 153 to 206). The RNA binding domain forms part of the top of the narrow conical area of the connector, a flexible region that undergoes structural changes during viral morphogenesis. The DNA binding domain is located not far away, 2-3 nm below, in the outer side of the narrow conical part. The precise location of the functional domains of the connector, as well as their relative positions provide the first experimental framework for understanding the connector function.

Amino Acid Sequence↗
PubMed1999

Simultaneous determination of tramadol and its major active metabolite O-demethyltramadol by high-performance liquid chromatography with electrochemical detection.

A novel, highly sensitive method was developed for simultaneous determination of tramadol and its main active metabolite O-demethyltramadol (ODMT) in rat plasma. The method involves a single-step extraction procedure and a specific determination by high-performance liquid chromatography with electrochemical detection, using an ethoxy analogue of tramadol (L-233) as internal standard. The dual-electrode detector was operated in the oxidation-screening mode. Absolute recoveries of tramadol and ODMT were about 80%. Calibration curves were linear over a concentration range of 10-1000 ng/ml for ODMT and 10-10000 ng/ml for tramadol with intra- and inter-day coefficients of variation not exceeding 10% and 15%, respectively. The limit of quantification for tramadol and ODMT was lower than 15 ng/ml and 10 ng/ml using 100 microl of plasma, respectively. The described method allows an adequate characterization of the plasma vs. time profiles for both compounds.

Analgesics, Opioid↗
PubMed1999

Enantiomeric separation of tramadol and its active metabolite in human plasma by chiral high-performance liquid chromatography: application to pharmacokinetic studies.

A sensitive and stereoselective high-performance liquid chromatographic assay for the quantitative determination of the analgesic tramadol and O-demethyltramadol, an active metabolite, is described in this work. Ketamine was used as internal standard. The assay involved a single tert-butymethylether extraction and liquid chromatography analysis with fluorescence detection. Chromatography was performed at 20 degrees C on a Chiracel OD-R column containing cellulose tris-(3,5-dimethylphenylcarbamate) as stationary phase, preceded by an achiral end-capped C18 column. The mobile phase was a mixture of phosphate buffer (containing sodium perchlorate (0.2 M) and triethylamine (0.09 M) adjusted to pH 6) and acetonitrile (80:20). The method developed was validated. The limit of quantitation of each enantiomer of tramadol and its active metabolite by this method was 0.5 ng/mL; only 0.5 mL of the plasma sample was required for the determination. The calibration curve was linear from 0.5 to 750 ng/mL for tramadol enantiomers, and from 0.5 to 500 ng/mL for O-demethyltramadol enantiomers. Intra and interday precision [coefficient of variation (CV)] did not exceed 10%. Mean recoveries of 95.95 and 97.87% for (+)R,R- and (-)S,S-tramadol and 97.70 and 98.79% for (+)R,R- and (-)S,S-O-demethyltramadol with CVs < 2.15% were obtained. Applicability of the method was demonstrated by a pharmacokinetic study in normal volunteers who received 100 mg of tramadol by the intravenous route.

Analgesics, Opioid↗
PubMed1999

Do magnesium ions influence barium mucosal coating of the large bowel?

The aim of the present study was to verify whether the presence of magnesium in the colon lumen at the time of the double-contrast barium enema (DCBE) examination changes the quality of barium mucosal coating. The two members of 38 pairs of patients undergoing DCBE with a standardised technique were randomly subjected to bowel preparation with sennosides and magnesium sulphate, or sennosides and sodium sulphate. Mucosal coating, residual fluid and colon cleansing were assessed independently by three radiologists. The null hypothesis was tested by means of Wilcoxon's signed-rank test. Barium mucosal coating was judged to be better in the members to whom magnesium sulphate was administered (p = 0.0007). There was no difference in the amount of residual fluids (p = 0.3198). Colon cleansing was judged to be better in the members to whom sodium sulphate was administered (p = 0.0166). These results demonstrate, in a simple way, that magnesium ions increase barium coating of the colon mucosa in vivo. The underlying mechanisms (increase in viscosity of barium suspension through water subtraction owing to the hydrophilism of magnesium ions, or interactions with the polysaccharide additives) need further investigation. A first clinical application could be the integration of magnesium ions in a newly designed isotonic electrolyte solution containing polyethylene glycol for the oral colon wash-out.

Adult↗
PubMed1999

Bowel preparation for the double-contrast barium enema: how to maintain coating with cleansing?

AIM: Poor mucosal coating, due to excess of fluid in the colon lumen, is a problem when the oral lavage method (4 litres of an iso-osmotic saline solution containing polyethylene glycol) is used as a preparation for double-contrast barium enema. Our aim was to assess the value of prior administration of sennosides to obtain a clean colon with a reduced volume of polyethylene glycol (PEG)-saline solution, but maintaining good mucosal coating. MATERIALS AND METHODS: After a 2-day low-residue diet, three different oral preparations were compared: (i) 4 litres of a PEG-saline solution (SELG) and 15 mg of bisacodyl (116 patients, SELG-4 group); (ii) 156 mg of sennosides, 15 g of magnesium sulphate, and 2 litres of water (116 patients, SennMg group); (iii) 156mg of sennosides and 2 litres of SELG (116 patients, SennSELG group). Compliance, complaints, cleansing, mucosal coating, and fluid retention were evaluated. RESULTS: Compliance was > 94% in every group. A higher percentage of mild nausea was observed in SELG-4 group, of mild abdominal cramping in SennMg group, of substantial abdominal cramping in SennSELG group (P < 0.02). Cleansing was better in SennSELG than in both the SELG-4 (P = 0.0003) and SennMg (P = 0.0353) group. Mucosal coating was better in SennMg than both SELG-4 (P = 0.0034) and SennSELG (P < 0.0001) group. There was more residual fluid in the SennSELG group than both in SELG-4 (P = 0.0029) and SennMg (P = 0.0059) group. CONCLUSION: For colon cleansing, the combination of sennosides and PEG-saline solution was better than either the 4 litre PEG protocol or the combination of sennosides and magnesium sulphate. For mucosal coating, the protocol combining sennosides and magnesium sulphate was more effective than either protocols using the PEG-saline solution. This may be due to the interaction of residual magnesium ions in the colon lumen with the barium suspension.

Aged↗
PubMed1999

IHF protein inhibits cleavage but not assembly of plasmid R388 relaxosomes.

Relaxosomes are specific nucleoprotein structures involved in DNA-processing reactions during bacterial conjugation. In this work, we present evidence indicating that plasmid R388 relaxosomes are composed of origin of transfer (oriT) DNA plus three proteins TrwC relaxase, TrwA nic-cleavage accessory protein and integration host factor (IHF), which acts as a regulatory protein. Protein IHF bound to two sites (ihfA and ihfB) in R388 oriT, as shown by gel retardation and DNase I footprinting analysis. IHF binding in vitro was found to inhibit nic-cleavage, but not TrwC binding to supercoiled DNA. However, no differences in the frequency of R388 conjugation were found between IHF- and IHF+ donor strains. In contrast, examination of plasmid DNA obtained from IHF- strains revealed that R388 was obtained mostly in relaxed form from these strains, whereas it was mostly supercoiled in IHF+ strains. Thus, IHF could have an inhibitory role in the nic-cleavage reaction in vivo. It can be speculated that triggering of conjugative DNA processing during R388 conjugation can be mediated by IHF release from oriT.

Bacterial Proteins↗
PubMed1999

Selection of antibody probes to correlate protein sequence domains with their structural distribution.

We propose a new approach that permits correlation of specific domains defined by their primary sequence with their location in the structure of complex macromolecular aggregates. It is based on the combination of well-established structural analysis methods that incorporate the use of overlapping peptides on cellulose membranes for the isolation and purification of specific antibodies from a polyclonal antiserum. Monospecific antibodies to the connector protein of bacteriophage phi29 were isolated from polyclonal antisera using a new development of the spotscan method. These antibodies can be purified in quantities that allow antigenicity testing in enzyme-linked immunosorbent assays, Western blotting and immunoprecipitations, demonstrating the specificity of this isolation procedure. This approach has allowed us to generate direct antibody probes for immunoelectron microscopy mapping of different connector protein domains in a low resolution three-dimensional epitope map.

Amino Acid Sequence↗
PubMed1999

Twice vaccinated recipients are better protected against epidemic measles than are single dose recipients of measles containing vaccine.

OBJECTIVE: To study measles risk after revaccination. DESIGN: A population-based case-control study during an epidemic season. MAIN OUTCOME MEASURE: Relative serologically confirmed measles risk. PARTICIPANTS AND METHODS: 153 vaccinated cases, mostly from rural areas, were serologically confirmed as measles at the central laboratory in 1988-89. A randomly selected group of 453 controls from either municipalities of vaccinated cases or from areas where measles attack rate was > 600/10(5), was identified via the population registry. Vaccination and measles histories of cases and controls were determined from official vaccination cards. RESULTS: Once and twice vaccinated had crude relative risk 15.6 and 2.3 compared with thrice vaccinated. When cases who had received their first vaccination at less than 14 months of age were omitted from analysis, once vaccinated had 4.0 (95% CI 1.2, 16.6) times higher age adjusted measles risk compared with twice vaccinated. When, omission was extended to cases from one particular municipality where even revaccinees had high measles risk during an explosive outbreak the corresponding risk ratio was 17.8 (2.8, 67.8). CONCLUSIONS: Twice vaccinated have better protection against epidemic measles compared with single dose recipients.

Adolescent↗
PubMed1999

Altered plasma and brain disposition and pharmacodynamics of methadone in abstinent rats.

The pharmacokinetics and pharmacodynamics of methadone were investigated in control and abstinent rats. Minipumps filled with saline (control group) or saline-morphine (abstinent group) solutions were used to induce physical dependence. Solutions were delivered continuously by minipumps for 6 days. The physical dependence was evaluated 12 h after minipump removal by measuring specific withdrawal signs. Animals from the abstinent group showed clear withdrawal signs such as hostility on handling and weight loss. Plasma and brain disposition and pharmacodynamics of methadone were evaluated after a 0.35 mg/kg i.v. bolus dose administered 12 h after minipump removal. Plasma clearance, distribution clearance, and volume of distribution at steady-state were significantly decreased (P < 0.05) in the abstinent group. Plasma levels of alpha1-acid glycoprotein and plasma protein binding were significantly increased (P < 0.05) in the abstinent group. The estimates of pharmacokinetic parameters based on unbound plasma concentrations did not differ between groups, with the sole exception of the unbound apparent volume of distribution. The access of methadone to the brain was significantly faster (P < 0.05) in the abstinent group, although the extent of distribution in the brain was diminished in comparison with the control group. Analgesia recorded with tail-flick was used as the pharmacodynamic endpoint. Analgesic response and effect compartment concentrations of methadone were related by the sigmoidal Emax model. Estimates of C50 [steady-state plasma concentrations eliciting half of maximum effect (Emax)]] based on unbound concentrations did not differ between groups. On the other hand, the estimate of Emax had decreased by 65% in the abstinent group.

Analgesics, Opioid↗
PubMed1998

Explosive school-based measles outbreak: intense exposure may have resulted in high risk, even among revaccinees.

Even high levels of measles vaccination coverage have not always prevented outbreaks of measles spread by airborne transmission. It has been suggested that a large inoculum might increase vaccine failure risk. Airbome transmission might occasionally entail a large measles inoculum. The epidemiologic relevance of measles among properly vaccinated persons (i.e., those vaccinated after 15 months of age and with live attenuated virus) is increased when they become contagious. The authors studied inoculum intensities as measured by proxy variables and the contagiousness of properly vaccinated persons who contracted measles among 51 measles patients infected in one school, at home, or elsewhere, utilizing preexisting records of measles cases and 214 healthy controls from an explosive school outbreak that occurred in a rural Finnish municipality in 1989. One "super-spreader" infected 22 others in one day, including eight once-vaccinated students and one twice-vaccinated student, probably during an assembly of 144 students in a poorly ventilated hallway with no sunlight. Those infected later at home had high measles risk, even if they were revaccinees. When siblings shared a bedroom with a measles case, a 78 percent risk (seven out of nine children) was observed among vaccinees. Vaccinees had approximately 2 days' shorter incubation time than unvaccinated persons. Vaccinated and unvaccinated students were equally able to infect their siblings. Total protection against measles might not be achievable, even among revaccinees, when children are confronted with intense exposure to measles virus.

Adolescent↗
PubMed1998

Duplex Doppler analysis of interlobular arteries in transplanted kidneys.

The aim of our study was to analyze changes in spectral Doppler waveforms between interlobar and interlobular arteries in renal transplants and to determine whether sampling location at interlobular level can be suitable for intrarenal resistive index (RI) measurements. Paired series of spectral tracings from interlobar arteries and respective interlobular branches were obtained in 62 consecutive renal transplants at 6.5-MHz Doppler frequency. The values of peak systolic velocity (PSV), end diastolic velocity (EDV) and RI were significantly (P < 0.01) reduced when calculated at interlobular level. In 38 % of cases, an interlobar RI higher than 0.70 corresponded to a normal interlobular RI. The values of PSV, EDV, and RI did not differ significantly at interlobular level between allograft subsets with normal and elevated serum creatinine level. Both intra- and interobserver variation were higher at interlobular than at interlobar level when performing the RI. During a conventional study of renal vasculature, an underestimation of abnormal RI findings can be expected from the incidental evaluation of interlobular tracings. We recommend sonologists to pay attention in accurately locating the sample volume at interlobar-arcuate level when evaluating intrarenal RI.

Adult↗
PubMed1998

Vaccine-induced measles virus antibodies after two doses of combined measles, mumps and rubella vaccine: a 12-year follow-up in two cohorts.

In Finland, a two-dose vaccination programme against measles, mumps and rubella (MMR) was begun in 1982. The programme with high coverage (97-98%) has eliminated these three diseases from Finland. The aim of the present study was to follow up the kinetics of measles virus antibodies in MMR vaccinated cohorts. We have followed the kinetics of measles virus antibody levels induced by vaccination in the same individuals immunized with their first MMR vaccine in 1982. After 12 years 80% of the original children remained available for sampling. Antibodies to measles virus were measured by haemagglutination inhibition (HI) and plaque reduction neutralization (NT) techniques. The primary dose induced 99.4% seroconversion for measles with a geometric mean HI antibody titre (GMT) of 1/269 (+/- 219), equivalent to 4304 mIU (milli-International Units) ml-1 in group A. The 12-year follow-up specimens showed a measles seropositivity rate of 100% as assayed with the HI and NT tests with a mean HI antibody titre of 1/39 (+/- 54), equivalent to 624 mIU ml-1. The vaccination-induced measles virus antibodies decline in the absence of natural booster infections. It is important to follow how long the protection achieved by the present vaccine programme will last after elimination of indigenous measles.

Antibodies, Viral↗
PubMed1998

Power Doppler sonography: clinical applications.

OBJECTIVE: Color Doppler imaging (CD) has had a great impact on ultrasonography (US). This technique depicts local flow by encoding an estimate of the mean Doppler frequency shift at a particular position in color. However, the choice of the mean frequency shift as the parameter for representing flow in color Doppler is somewhat arbitrary. Power Doppler ultrasound is a technique that encodes the power in the Doppler signal in color. This parameter is fundamentally different from the mean frequency shift. The frequency is determined by the velocity of the red blood cells, while the power depends on the amount of blood present. Providing an image of a different property of blood flow, power Doppler has shown several key advantages over colour Doppler, including higher sensitivity to flow, better edge definition and depiction of continuity of flow. In this paper we review the results of power Doppler clinical studies. MATERIALS AND METHODS: All relevant information available in the literature on the potential clinical applications of this technique was revised to give a detailed survey. RESULTS: The increased flow sensitivity and better vascular detailing of power Doppler have been used to detect flow presence and characteristics in vessels that are poorly imaged with conventional color Doppler. The improved depiction of tissue vasculature has shown potential advantages, especially in some areas, such as the cortex of native kidneys and renal allografts, the prepuberal testis, the infant hip and the bowel wall, in which color Doppler is not sensitive enough to detect clinically important, slow and poor flow in small vessels. In inflammatory conditions, power Doppler was valuable in depicting increased flow in vessels that are dilated because of inflammatory response. In this field, advantages have been reported in acute cholecystitis and in inflammatory states of musculoskeletal tissues. The higher sensitivity to slow flow and the improved detailing of the course of tortuous and irregular vessels made power Doppler a promising technique to image intratumoral vessels and, thereby, to ameliorate the accuracy of color Doppler in predicting the likelihood of benign versus malignant nature of nodules. Specific flow patterns, missed at color Doppler studies, have been indicated with power Doppler in some tumors of the liver and breast. In different settings, power Doppler also permitted to monitor serial blood flow changes after therapy and to display them as color intensity, allowing the observer to distinguish flow changes. CONCLUSION: Although the actual role of power Doppler in changing patient management has not been assessed yet, this technique can depict flow which was previously undetectable, and thus permits an easier and more confident diagnosis in body regions where the ultrasound signal is weak because blood vessels are small.

Blood Vessels↗