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Biomedical subjects

M Pérez

Publications and source records attributed to M Pérez.

At least 19 recordsLinked to original sources
PubMed2004

Characterization by atomic force microscopy of Alzheimer paired helical filaments under physiological conditions.

Paired helical filaments (PHF) is an aberrant structure present in the brain of Alzheimer's disease patients which has been correlated with their degree of dementia. In order to determine the structure of PHF, several studies have been performed using atomic force microscopy (AFM). However, those studies have the limitation that they have not been done in solution and the sample could be far from the real physiological conditions. In this work we present an AFM analysis of PHF in liquid environment and we compare that analysis with that performed in dry conditions. PHF imaging in liquid was only possible by using jumping mode AFM as the imaging technique. Jumping mode AFM images of PHF in solution show first, a notable increase in the absolute values of the height of the filament, and second, a smaller ratio between the height measured at the upper and at the lower part of the PHF. Direct comparison of the experimental data with structural models has been performed. From this we conclude that the PHF structure is compatible with two coupled ribbons with an overall height of 20 nm and a width of 10 nm.

Body Fluids↗
PubMed2004

Effects of the rotor pedalling system on the performance of trained cyclists during incremental and constant-load cycle-ergometer tests.

The aim of this study was to determine the effects of Rotor, a new cycle crank configuration that effectively allows the pedals to move independently throughout the duty cycle, on indices of endurance cycling performance in trained cyclists. Ten cyclists (5 Rotor users and 5 non-users; age (mean +/- SD): 22 +/- 5 y; VO(2)max: 69.5 +/- 5.1 mL. kg(-1).min(-1)) volunteered to participate in the study. On four separate days, the subjects performed four cycle-ergometer tests, i.e. two incremental tests and two 20-min tests. An imposed crank rate of 75 rev.min(-1) was used during all tests. The incremental protocol started at 112.5 W, and the power output was increased by 37.5 W every 3 min until volitional exhaustion. The 20-min tests were performed at a fixed power output equivalent to 80 % of the highest power output that the cyclists maintained for a complete 3-min period during incremental tests. Both types of tests were performed with the conventional crank system and the Rotor following a counter-balanced, cross-over design. Gas exchange parameters were measured in all the tests and blood lactate was determined at the end of each 3-min period (incremental tests) and at the end of the 20-min tests. A three factor (pedalling system used during the tests x habitual pedalling system x power output [incremental tests] or time [20-min tests]) ANOVA with repeated measures on power output (incremental tests) or time (20-min tests) was used to analyse several indices of performance, e.g. peak power output, VO(2)max, lactate threshold, onset of blood lactate accumulation, economy, delta, and gross efficiency. No differences (p > 0.05) were found between the Rotor and conventional systems for any of the aforementioned variables. It seems that the theoretical advantage brought about by the Rotor system, i.e. improved contra-lateral cooperation of both legs, would be minimized in trained cyclists. Although field studies are needed to assess the possible implications, in terms of actual racing, of the new system, commonly used indicators of endurance cycling performance do not seem to be improved with the Rotor in trained cyclists.

Adult↗
PubMed2004

Which laboratory variable is related with time trial performance time in the Tour de France?

OBJECTIVE: To investigate the relationship between several physiological variables that can be easily obtained during cycle ergometer gradual testing (for example, peak power output (W(peak)), Vo(2max), or ventilatory threshold (VT)) and actual (>50 km) time trials (TT) time performance during the Tour de France. METHODS: We collected data in professional cyclists from the first TT of the 1998 Tour de France (TT1, 58 km distance; n = 6 cyclists) and the first (TT2, 56.5 km; n = 5) and second TT of the 1999 Tour de France (TT3, 57 km; n = 5). RESULTS: A negative relationship was found between power output (W) at VT (VT(Watt)) and TT final time (s) in TT1 (r = -0.864; p = 0.026; standard error of estimate (SEE) of 73 s; and 95% confidence limits (95% CL) -0.98; -0.18), TT2 (r = -0.77; p = 0.27; SEE of 139 s; and 95% CL -0.98; 0.35), and TT3 (r = -0.923; p = 0.025; SEE of 94 s; and 95% CL -1.00; -0.22). CONCLUSIONS: Actual performance in long TT during the Tour de France (>50 km distance, performed after at least 1-2 weeks of continuous competition), in which some cumulative fatigue inevitably occurs, is related, at least in part, to the power output that elicits the VT. No other routine physiological variable (for example, Vo(2max) or W(peak)) is related to performance in this type of event.

Adult↗
PubMed2004

Postinfectious diffuse proliferative glomerulonephritis and acute renal failure in an HIV patient.

Postinfectious proliferative glomerulonephritis may occur in HIV-infected patients, although it is not a common cause of severe acute renal failure in them. We report a woman with HIV infection, who developed hypocomplementemic acute nephritic syndrome 10 days after an upper respiratory infection. Systemic diseases were excluded. The serum creatinine level increased to 6.6 mg/dl. Renal biopsy showed diffuse endocapillary proliferative glomerulonephritis, with mesangial and capillary walls, granular deposits of IgG and C3 by immunofluorescence. She was given corticosteroids with progressive normalization of her renal function. No opportunistic infections have occurred during 1-year follow-up.

Acute Kidney Injury↗
PubMed2003

Bacteremia by Streptobacillus moniliformis: first case described in Spain.

Described here is the case of an 87-year-old man who developed fever, chills and discomfort caused by Streptobacillus moniliformis. This pathogen is one of the causes of rat-bite fever, an uncommon bacterial illness transmitted through a bite or scratch from a rodent or the ingestion of food or water contaminated with rat faeces. Cases of rat-bite fever are rarely reported in Spain. The patient reported no history of rat bite or rodent contact, and the only known risk factor was contact with a dog and a cat that were kept as pets. Streptobacillus moniliformis was isolated in two sets of blood cultures. This case represents what is believed to be the first report of bacteremia due to Streptobacillus moniliformis in Spain.

Aged↗
PubMed2003

The importance of clinical factors in parenteral nutrition-associated hypertriglyceridemia.

AIMS: The purpose of this study was to establish the relevance of several clinical factors associated with parenteral nutrition (PN) hypertriglyceridemia and to construct a predictive model for this complication. METHOD: This multicenter study included all patients with initial serum triglyceridemia <3 mmol and receiving a minimum of 7 days' PN therapy. The study ended for each patient when hypertriglyceridemia developed or PN was terminated. Two multivariate models were constructed, one to study the clinical factors and the second to predict plasma triglyceridemia. A total of 22 clinical factors studied as independent variables were included in the multiple-step regression models only when they showed a P-value over 0.1. Statistical significance was determined by the confidence interval of the odds ratio (OR) and the partial regression coefficient (b). RESULTS: The study included 260 patients from 14 hospitals. Lipid administration was 0.83+/-0.37 g/kg/day. Among the total, 68 patients (26.2%) showed hypertriglyceridemia. Variables included in both models were serum glucose (OR, 2.63; b, 0.06), renal failure (OR, 10.56; b, 1.70), corticoid administration >0.5 mg/kg (OR, 7.98; b, 0.97), pancreatitis (OR, 4.38; b, 0.64), sepsis (OR, 4.48; b, 0.24), lipids infused (OR, 3.03; b, 0.24) and heparin administration >3 mg/kg/day (OR, 0.11; b, -1.21). CONCLUSION: Although the rate of lipid infusion was low, certain clinical factors modified triglyceridemia. Nevertheless, relatively fast plasma clearance of lipids infused indicates that a reduction in lipid supply could be a quick, effective measure for controlling hypertriglyceridemia. Thus, careful monitoring of patients with clinical factors predicting risk in the model studied, with adjustment of lipid perfusion rates accordingly, is suggested to avoid hypertriglyceridemia.

Adult↗
PubMed2003

Effects of electrical stimulation on VO2 kinetics and delta efficiency in healthy young men.

OBJECTIVE: To determine the effects of electrical stimulation (ES) on oxygen uptake (VO(2)) kinetics and delta efficiency (DE) during gradual exercise. The hypothesis was that ES would attenuate the VO(2)-workload relation and improve DE. METHODS: Fifteen healthy, untrained men (mean (SD) age 22 (5) years) were selected. Ten were electrostimulated on both quadriceps muscles with a frequency of 45-60 Hz, with 12 seconds of stimulation followed by eight seconds recovery for a total of 30 minutes a day, three days a week for six weeks. The remaining five subjects were assigned to a control group. A standardised exercise test on a cycle ergometer (ramp protocol, workload increases of 20 W/min) was performed by each subject before and after the experimental period. The slope of the VO(2)-power output (W) relation (deltaVO(2)/deltaW) and DE were calculated in each subject at moderate to high intensities (above the ventilatory threshold-that is, from 50-60% to 100% VO(2)max). RESULTS: The mean (SEM) values for deltaVO(2)/deltaW and DE had significantly decreased and increased respectively after the six week ES programme (p<0.05; 9.8 (0.2) v 8.6 (0.5) ml O(2)/W/min respectively and 27.7 (0.9) v 31.5 (1.4)% respectively). CONCLUSIONS: ES could be used as a supplementary tool to improve two of the main determinants of endurance capacity, namely VO(2) kinetics and work efficiency.

Adult↗
PubMed2003

Henoch-Schönlein purpura associated with clarithromycin. Case report and review of literature.

OBJECTIVE: To report a case of Henoch-Schönlein purpura that appears to be related to the intake of clarithromycin for pharyngitis/tonsillitis. CASE SUMMARY: We describe a case of Henoch-Schönlein associated with clarithromycin therapy in a 48-year-old white man with no history of allergic drug reactions. Four days after starting therapy, he came to our hospital emergency room because of a non-pruritic palpable purpuric rash on the trunk and extremities and arthralgias involving elbows and knees. Administration of clarithromycin was suspended, in a few days, arthralgias and skin lesions quickly resolved. Three weeks later, the patient presented again with abdominal pain, dark-red urine and swelling of the legs. Urinalysis revealed proteinuria of 11 g/24 h and hematuria. A percutaneous renal biopsy showed a diffuse endocapillary proliferative glomerulonephritis with segmental areas of fibrinoid necrosis within glomeruli, on immunofluorescence study granular deposits of IgA and C3 were present in the mesangium and capillary walls. A diagnosis of HSP was made. We suspected that the causative agent might be clarithromycin since this was the only drug added before the cutaneous and renal condition appeared. CONCLUSIONS: Our case and the previous case suggest that HSP may represent a potential adverse effect of clarithromycin, clinicians should be alerted to this potentially severe side effect of such a widely used drug. In accordance with the data obtained and based on the Naranjo algorithm, the adverse reaction could be considered possible.

Anti-Bacterial Agents↗
PubMed2002

Chromatographic removal combined with heat, acid and chaotropic inactivation of four model viruses.

The virus removal of protein A affinity chromatography, inactivation capacity, acid pH and a combination of high temperature with a chaotropic agent was determined in this work. The model viruses studied were sendaivirus, human immunodeficency virus (HIV-IIIb), human poliovirus type-II, human herpesvirus I and canine parvovirus. The protein A affinity chromatography showed a maximum reduction factor of 8 logs in the case of viruses larger than 120 nm size, while for small viruses (18-30 nm) the maximum reduction factor was about 5 logs. Non viral inactivation was observed during the monoclonal antibody elution step. Low pH treatment showed a maximum inactivation factor of 7.1 logs for enveloped viruses. However, a weak inactivation factor (3.4 logs) was obtained for DNA nonenveloped viruses. The combination of high temperature with 3 M KSCN showed a high inactivation factor for all of the viruses studied. The total clearance factor was 23.1, 15.1, 13.6, 20.0 and 16.0 logs for sendaivirus, HIV-IIIb, human poliovirus type-II, human herpesvirus I and canine parvovirus, respectively.

Animals↗
PubMed2002

Catecholamine-beta-alanyl ligase in the medfly Ceratitis capitata.

Dopamine (DA) and norepinephrine (NE) derivatives play an important role in the sclerotization and pigmentation of insect cuticles by serving as precursors for cuticular cross-linking. Protein preparations from prepupae of the medfly, Ceratitis capitata, were able to conjugate beta-alanine with DA producing N-beta-alanyldopamine (NBAD) or with NE, synthesizing N-beta-alanylnorepinephrine (NBANE). The latter reaction has been demonstrated for the first time. Apparent kinetic parameters were obtained for both substrates, DA (V(max)=30.7+/-6.0 pmol min(-1) mg(-1); K(m)=29.5+/-3.5 microM) and NE (V(max)=16.1+/-6.6 pmol min(-1)mg(-1); K(m)=89.0+/-8.3 microM). The same protein seems to be responsible for both enzymatic activities, judging from several criteria like identical behavior under heat inactivation as well as identical Mg2+ and Mn2+ dependent stimulation and Co2+ inhibition. Furthermore, the melanic mutants niger of C. capitata and ebony(4) of D. melanogaster, known to be defective for NBAD synthase, were also unable to synthesize NBANE. The protein preparation acylated tyrosine with much less efficiency, to produce sarcophagine (beta-alanyltyrosine). Strikingly, extracts from the melanic mutants were unable to synthesize sarcophagine. Our results strongly suggest that the enzymatic activity previously known as NBAD synthase is in fact a novel catalytic protein showing broad substrate specificity. We propose to identify it as catecholamine-beta-alanyl ligase.

Animals↗
PubMed2002

Feasibility trial of methotrexate-paclitaxel as a second line therapy in advanced urothelial cancer.

To evaluate the clinical value of the concurrent use of methotrexate administered immediately before paclitaxel, we investigated the efficacy and toxicity of this two-drug combination administered as palliative second line therapy in patients with advanced urothelial cancer. The design of the schedule and sequence used was based on our previous preclinical data from a comparative study on sequential combinations of paclitaxel and methotrexate in a human bladder cancer cell line. As a confirmation study, we further extended our analysis of in vitro synergism. Twenty patients with advanced transitional cell carcinoma of the urinary tract previously treated with platinum-based therapy, with adequate renal function and a performance status > or = 60 were considered eligible. They received therapy with methotrexate 30 mg/m2 administered as an intravenous bolus, followed immediately by paclitaxel 175 mg/m2 given as a 3-hr infusion, both on day 1 every 21 days. Therapy was given on a compassionate-use basis until either disease progression was documented or the patient became intolerant to therapy. In vitro data were further analyzed using the median-effect principle and the combination index method. Twenty patients with metastatic (16 patients) or locally advanced disease (four patients) received a median of three cycles of therapy. Of the 19 patients assessable for response, there were six partial responses and seven disease stabilizations with no complete responses. Median duration of response was 3 months (range, 2-7) and median survival was 5 months. Three patients developed grade 3-4 neutropenia, one patient had grade 3 anemia, four patients had grade 2-3 sensory neuropathy, and three patients had myalgias. Eighteen patients developed alopecia. Gastrointestinal toxicity was mild. One patient died after the first cycle due to pulmonary thrombo-embolism and could not be evaluated for response. The synergistic in vitro effect of the concurrent combination was confirmed in analyses performed under mutually exclusive and mutually nonexclusive criteria. In conclusion, the combination of methotrexate and paclitaxel at this dose and sequence is feasible and active as a palliative therapy in patients with advanced urothelial cancer previously treated with platinum-based therapies. This schedule merits further investigation in a phase-II trial.

Adenocarcinoma↗
PubMed2002

Lactic acidosis, potassium, and the heart rate deflection point in professional road cyclists.

OBJECTIVE: To determine the influence of lactic acidosis, the Bohr effect, and exercise induced hyperkalaemia on the occurrence of the heart rate deflection point (HRDP) in elite (professional) cyclists. METHODS: Sixteen professional male road cyclists (mean (SD) age 26 (1) years) performed a ramp test on a cycle ergometer (workload increases of 5 W/12 s, averaging 25 W/min). Heart rate (HR), gas exchange parameters, and blood variables (lactate, pH, P(50) of the oxyhaemoglobin dissociation curve, and K(+)) were measured during the tests. RESULTS: A HRDP was shown in 56% of subjects at about 88% of their maximal HR (HRDP group; n = 9) but was linear in the rest (No-HRDP group; n = 7). In the HRDP group, the slope of the HR-workload regression line above the HRDP correlated inversely with levels of K(+) at the maximal power output (r = -0.67; p<0.05). CONCLUSIONS: The HRDP phenomenon is associated, at least partly, with exercise induced hyperkalaemia.

Acidosis, Lactic↗
PubMed2001

Polar targeting of Shigella virulence factor IcsA in Enterobacteriacae and Vibrio.

Asymmetric localization is key to the proper function of certain prokaryotic proteins important to virulence, chemotaxis, cell division, development, motility, and adhesion. Shigella IcsA is localized to the old pole of the bacterium, where it mediates assembly of an actin tail inside infected mammalian cells. IcsA (VirG) is essential to Shigella intracellular motility and virulence. We used translational fusions between portions of IcsA and the green fluorescent protein (GFP) to determine the regions of IcsA that are necessary and sufficient for its targeting to the bacterial old pole. An IcsA-GFP fusion that lacks a signal peptide localized to the old pole, indicating that signal peptide-mediated secretion is not required for polar localization. Two regions within IcsA were required for localization of an IcsA-GFP fusion to the old pole. Further characterization of these regions indicated that amino acids 1-104 and 507-620 were each independently sufficient for polar localization. Finally, when expressed in Escherichia coli, Salmonella typhimurium, Yersinia pseudotuberculosis, and Vibrio cholerae, each of the two targeting regions localized to the pole, indicating that the mechanism of polar targeting used by IcsA is present generally among Enterobacteriacae and Vibrio.

Amino Acid Sequence↗
PubMed2001

In vitro assembly of tau protein: mapping the regions involved in filament formation.

Unraveling the mechanism of self-assembly of the protein tau into paired helical filaments (PHFs) is a crucial step toward the understanding of Alzheimer's and other neuropathological diseases at the molecular level. In an effort to map the role of different regions of tau in the mechanism of self-assembly, we have studied the polymerization ability of different tau fragments using an in vitro assay. Our results indicate that the N-terminal domain interferes with tau's ability to polymerize in vitro. The effect seems to be size dependent. Particularly, an isoform of tau from the peripheral nervous system, which has a much larger N-terminal domain, was found unable to form filaments in our in vitro assay. This finding can explain why in Alzheimer's patients PHFs only accumulate in the neurons from the central nervous system. We also report that a short segment of tau located in the third microtubule binding repeat (residues 317 to 335, peptide 1/2R) is probably the minimal segment of that region able to grow into filaments in vitro and in the presence of heparin. In contrast with whole peptide 1/2R, peptides corresponding to either the N-terminal or C-terminal halves of this segment were unable to form filaments. Finally, our polymerization studies of peptides from the C-terminal domain reveal a short sequence spanning residues 391 to 407 that grows into filaments in vitro. This tau segment forms filaments regardless of whether is incubated with heparin. Moreover, such filaments differ in diameter and morphology, suggesting a different mechanism of self-assembly.

Actin Cytoskeleton↗
PubMed2001

[Alcohol consumption among students of a health area. Habits and beliefs].

OBJECTIVES: 1. To describe the habits and conduct of school students (13-17 years old) around alcohol in the Cartagena Health Area. 2. To discover the factors underlying consumption. 3. To analyse beliefs and behaviour about consumption. DESIGN: Cross-sectional descriptive study. SETTING: Health area. PARTICIPANTS: 16,657 school students. Sample population (n = 1004). Large-group sampling (sampling unit: class-room), accuracy = 3%, CI = 95%, p = q = 50%, stratified by school and geographical area. MEASUREMENTS AND MAIN RESULTS: Anonymous, self-filled questionnaire (33 open and closed questions). SELECTION CRITERIA: attendance at class on the day of the questionnaire. VARIABLES: social, economic and cultural data on parents and students, course, type of family, alcohol consumption (starting age, access, individual habits, friends and family), beliefs about consumption, study profile of consumer. STATISTICAL ANALYSIS: description of variables, chi-squared test, t test, logistical regression. 99.2% filled in the questionnaire. Students' average age was 15.84 (SD, 1.21). 89.96% lived with their parents. 83.4% had consumed alcohol on some occasion, with no relationship to current consumption (p > 0.05). Starting age was 13.77 (SD, 1.78), 48.5% in discos/bars and 19% at home (p > 0.05). 47.5% had got drunk on some occasion (p > 0.05). 88.2% customarily drank alcohol mixed with other drinks (p > 0.05). 51.8% drank at week-ends (2.4% every day) (p > 0.05). 63.3% thought it easy to acquire drinks: 48.9% in supermarkets, 26.4% at petrol stations (p = 0.038). 71% of consumers agreed that "alcohol is a drug" (p = 0.005). 13% believed "it does not cause dependency" (p = 0.00001). 23.3% thought that it is not true to say "the person who does sport is healthier and does not take alcohol". CONCLUSIONS: The pattern of consumption is similar to that found in other autonomous communities, although in greater quantity and without differences in kind. Mean age of consumer: 15 years old. They usually drink alcohol mixed with other soft drinks, normally at week-ends. They are very ignorant of the effects of consumption.

Adolescent↗
PubMed2001

Conjugate addition of organocuprates to chiral bicyclic delta-lactams. Enantioselective synthesis of cis-3,4-disubstituted and 3,4,5-trisubstituted piperidines.

[reaction: see text] Chiral nonracemic bicyclic lactam 3, easily accessible by cyclodehydration of (R)-phenylglycinol and racemic methyl 4-formylhexanoate, was converted to the unsaturated lactams 5, which undergo the stereoselective conjugate addition of lower order cyanocuprates to ultimately lead to enantiopure cis-3,4-disubstituted and 3,4,5-trisubstituted piperidines.

Heterocyclic Compounds, 2-Ring↗