Search

We analyzed a possible association between RUNX3 gene polymorphisms and haplotypes in Mexican patients with colorectal cancer (CRC). Genomic DNA samples were obtained from the peripheral blood of 176 Mexican patients with CRC at diagnosis and from 195 individuals that formed the control group. The polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism. Association was estimated by odds ratio (OR). The haplotypes and linkage disequilibrium were established using the Arlequin v3.5 software. We found that the RUNX3 polymorphisms analyzed were in Hardy-Weinberg equilibrium. The RUNX3 rs2236852 AA genotype and A allele showed association with CRC (OR = 0.39, 95%CI = 0.21-0.73, P < 0.01; OR = 0.65, 95%CI = 0.49-0.87, P < 0.01, respectively), while the rs6672420, rs11249206, and rs760805 polymorphisms did not show significant association with CRC. The TA haplotype (SNPs rs760805 and rs2236852) showed an increased risk for CRC (OR = 2.52, 95%CI = 1.47-4.30, P < 0.001). In conclusion, we found that the AA genotype and A allele of rs2236852 polymorphism confer a decreased CRC risk, while the TA haplotype appears to increase the risk of CRC development in Mexican patients.

We study experimentally a four-winged flapping flyer with chord-wise flexible wings in a self-propelled setup. For a given physical configuration of the flyer (i.e. fixed distance between the forewing and hindwing pairs and fixed wing flexibility), we explore the kinematic parameter space constituted by the flapping frequency and the forewing-hindwing phase lag. Cruising speed and consumed electric power measurements are performed for each point in the \((f,\varphi )\) parameter space and allow us to discuss the problem of performance and efficiency in four-winged flapping flight. We show that different phase-lags are needed for the system to be optimised for fastest flight or lowest energy consumption. A conjecture of the underlying mechanism is proposed in terms of the coupled dynamics of the forewing-hindwing phase lag and the deformation kinematics of the flexible wings.

A selection of lactoferricin B (LfcinB)-related peptides with an angiotensin I-converting enzyme (ACE) inhibitory effect have been examined using in vitro and ex vivo functional assays. Peptides that were analyzed included a set of sequence-related antimicrobial hexapeptides previously reported and two representative LfcinB-derived peptides. In vitro assays using hippuryl-L-histidyl-L-leucine (HHL) and angiotensin I as substrates allowed us to select two hexapeptides, PACEI32 (Ac-RKWHFW-NH 2 ) and PACEI34 (Ac-RKWLFW-NH 2 ), and also a LfcinB-derived peptide, LfcinB 17-31 (Ac-FKCR-RWQWRMKKLGA-NH 2 ). Ex vivo functional assays using rabbit carotid arterial segments showed PACEI32 (both D- and L-enantiomers) and LfcinB 17-31 have inhibitory effects on ACE-dependent angiotensin I-induced contraction. None of the peptides exhibited in vitro ACE inhibitory activity using bradykinin as the substrate. In conclusion, three bioactive lactoferricin-related peptides exhibit inhibitory effects on both ACE activity and ACE-dependent vasoconstriction with potential to modulate hypertension that deserves further investigation.

The influence of alloxan-induced diabetes on the reactivity of rabbit basilar artery to endothelin-1 was examined. Endothelin-1 induced concentration-dependent contraction of basilar arteries that was higher in diabetic than in control rabbits. Endothelium removal produced a higher enhancement of the endothelin-1-induced contraction in control than in diabetic rabbits. N(G)-nitro-L-arginine (L-NOArg) enhanced the maximal contraction induced by endothelin-1 in control rabbits and potentiated this response in diabetic rabbits. Endothelin ETA receptor antagonist, cyclo(D-Asp-Pro-D-Val-Leu-D-Trp) (BQ-123), inhibited endothelin-1-induced contraction in both rabbit groups. Endothelin ETB receptor antagonist, 2,6-Dimethylpiperidinecarbonyl-gamma-Methyl-Leu-Nin-(Methoxycarbonyl)-D-Trp-D-Nle (BQ-788), enhanced endothelin-1-induced contraction in control rabbits and decreased the potency of endothelin-1 in diabetic rabbits. Sodium nitroprusside-induced relaxation of basilar arteries was lower in diabetic than in control rabbits. These results suggest that mechanisms underlying rabbit basilar artery hyperreactivity to endothelin-1 include decreased endothelial modulation of endothelin-1-induced contraction, with impaired endothelial endothelin ETB receptor activity; decreased sensitivity to nitric oxide (NO) in vascular smooth muscle; and enhanced participation of muscular endothelin ETA and ETB receptors.

Aunque la educación ha constituido siempre un componente esencial de la profesión médica, su desarrollo explícito y específico sólo se ha iniciado en las últimas décadas. La investigación en educación médica está todavía en una etapa muy inicial de su desarrollo. Las intervenciones educativas son habitualmente complejas y de carácter cualitativo; resulta, por ello, difícil, aunque indispensable, obtener evidencias científicas que avalen tanto los diversos métodos educativos utilizados como los instrumentos de evaluación que se emplean en los diferentes niveles de la formación médica. A partir de la perspectiva y de las estrategias generadas por las metodologías de la medicina basada en la evidencia, ha surgido recientemente la Colaboración EMBE como una red internacional que tiene como objetivo prioritario recoger y promover el despliegue de la mejor evidencia de la cual se pueda disponer sobre el rigor y la calidad de los actuales y de los nuevos métodos educativos y evaluativos en el ámbito de la profesión médica, a fin de optimizar el uso de la extraordinaria inversión que realiza la sociedad en la formación de los profesionales en atención médica.Although education has ever constituted an essential component of medical profession, its explicit and specific development has only recently started in the last few decades. Research on medical education is still in a very initial stage of development. Educational interventions usually are complex and of a qualitative nature; that’s why it is hard, even though essential, to obtain scientific evidences that underpin the various educational methods as well as the assessment tools which are used at different medical education levels. From the perspective and strategies generated by evidence based medicine methodologies, The BEME Collaboration has recently emerged as an international network whose priority objective is to collect and to promote the best evidence that may be affordable on the rigor and quality of currently used and newly created formative and evaluative methods in the medical profession field, in order to optimise the use of the extraordinary investment that society carries out in training health care professionals.

Acid activated metakaolins (AAMKs) have been prepared by calcination of the natural clay at 600degreesC to provide a metakolin which was then leached at 80degreesC for 3 h using 1M, 2M, 3M, and 6M HCl. These materials were characterized and their ability to transform the off gases from HDPE decomposition into useful aromatic species was evaluated. The amount of adsorbed water and the number of acid sites increased with the severity of acid treatment, Variable temperature DRIFTS spectroscopy of pyridine treated samples revealed that both Brphinsted and Lewis acid centers were present until 425degreesC. Pyridine bonded to the Lewis acid centers was more thermally stable. The AAMKs were all selective to the production of toluene with respectable, but lesser, amounts of xylenes and trimethylbenzenes. This selectivity contrasts with that of acid leached and pillared smectites which are selective toward trimethylbenzene. (C) 2002 Elsevier Science (USA).

Transition from hospital to home is a vulnerable period for older adults with multiple chronic conditions. A pilot of the Transitional Care Model at a community hospital reduced readmission rates for patients with heart failure by 48%. This article shares the experience of a large metropolitan health care system in expanding transitional care across facilities to decrease readmission rates.

Colorectal cancer (CRC) is characterized by enhanced expression and activity of several metalloproteinases (MMPs), including MMP13 and MMP7, which play an important role in tumor invasion and metastasis. The objective of this study was to analyze the association of functional MMP7-181A/G and MMP13-77A/G promoter polymorphisms with susceptibility to CRC in a Mexican population. Genomic DNA samples were obtained from peripheral blood of 102 CRC patients and 125 blood donors who were included as the control group. Identification of polymorphisms was based on polymerase chain reaction-restriction fragment length polymorphism methodology. The association was estimated by the odds ratio (OR) test. The results showed that MMP7-181A/G and MMP13-77A/G variants were associated with CRC. For MMP7-181A/G, the AA (P=0.02, OR=3.38, 95% confidence interval (CI)=1.16-9.84) and AG (P=0.01, OR=3.4, 95%CI=1.17-9.83) genotypes were associated with an increased risk of CRC. For MMP13-77A/G, the AA and AG genotypes were associated with CRC (AA genotype: P=0.04, OR=3.2, 95%CI=1.004-10.2; AG genotype: P=0.01, OR=4.08, 95%CI=1.3-13.07). In conclusion, AA and AG genotype carriers for both polymorphisms are at a higher risk of developing CRC in this Mexican population.

By taking advantage of the extreme stability of a protein-DNA complex, we have obtained two highly specific monoclonal antibodies against a predetermined palindromic DNA sequence corresponding to the binding site of the E2 transcriptional regulator of the human papillomavirus (HPV-16). The purified univalent antibody fragments bind to a double-stranded DNA oligonucleotide corresponding to the E2 binding site in solution with dissociation constants in the low and subnanomolar range. This affinity matches that of the natural DNA binding domain and is severalfold higher than the affinity of a homologous bovine E2 C-terminal domain (BPV-1) for the same DNA. These antibodies discriminate effectively among a number of double- and single-stranded synthetic DNAs with factors ranging from 125- to 20,000-fold the dissociation constant of the specific DNA sequence used in the immunogenic protein-DNA complex. Moreover, they are capable of fine specificity tuning, since they both bind less tightly to another HPV-16 E2 binding site, differing in only 1 base pair in a noncontact flexible region. Beyond the relevance of obtaining a specific anti-DNA response, these results provide a first glance at how DNA as an antigen is recognized specifically by an antibody. The accuracy of the spectroscopic method used for the binding analysis suggests that a detailed mechanistic analysis is attainable. Fil: Cerutti, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Centeno, Juan M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Goldbaum, Fernando Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: de Prat Gay, Gonzalo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina

The role of gene induction (expression of HSP72 and c-JUN proteins) and delayed ischemic cell death (in situ labeling of DNA fragmentation) have been investigated in the goat hippocampus after transient global cerebral ischemia. The animals were subjected to 20-min ischemia (bilateral occlusion of the external carotid arteries plus bilateral jugular vein compression) and allowed to reperfuse for 2 h, and then 1, 3, and 7 days. Histological signs of cell loss were not found in the hippocampus at 2 h, 1 day, or 3 days of reperfusion. However, such an ischemic insult produced extensive, selective, and delayed degeneration in the hippocampus, as 68% of the neurons in CA1 had died at 7 days, but cell loss was not detected in CA3 and dentate gyrus fields. Concomitantly, a high percentage of TUNEL-positive CA1 neurons (60 ± 9%, mean ± SEM) was seen at 7 days, but not at the earlier time points. Mild induction of HSP72 was detected in the goat hippocampus after ischemia. The maximum percentage of HSP72-positive neurons (10–15%) was shown at 3 days of reperfusion and was concentrated mainly in the CA3 field, subiculum, and hilus, rather than in the CA1 field, whereas HSP72 expression was hardly detected at 7 days. At this later time point, scattered induction of nuclear c-JUN was found in a few neurons. The results show that: 1) postischemic delayed neuronal death selectively affects the CA1 field in the goat hippocampus, a phenomenon which seems to take longer to develop than in previously reported rodent models; and 2) postischemic expression of c-JUN does not appear to be related to cell death or survival, while the inability of most CA1 neurons to express HSP72 could contribute to neuronal death. Hippocampus 2001;11:146–156. © 2001 Wiley-Liss, Inc.

Nitric oxide (NO) plays a dual role (neuroprotection and neurotoxicity) in cerebral ischemia. NO promoting strategies may be beneficial shortly after ischemia. Therefore, we have studied the hemodynamic and possible neuroprotective effects of two NO donors, the classical nitrovasodilator sodium nitroprusside (SNP) and the NONOate spermine/NO, after transient focal cerebral ischemia in rats. Parietal cortical perfusion was measured by laser-Doppler flowmetry. The effects of increasing intravenous doses (10-300 microgram) of sodium nitroprusside and spermine/NO on cortical perfusion and arterial blood pressure were assessed. Transient (2 h) focal cerebral ischemia was carried out by the intraluminal thread method. The effects of intraischemic intravenous infusion of SNP (0.11, 1.1 mg/kg) and spermine/NO (0.36, 3.6 mg/kg) on hemodynamic parameters and infarct size developed after 1 week reperfusion were assessed. In control conditions, SNP and, to a lesser extent, spermine/NO induced dose-dependent hypotension and concomitant reduction in cortical perfusion. In focal cerebral ischemia, infusion of SNP (0.11 mg/kg) and spermine/NO (0.36, 3.6 mg/kg) reduced the infarct size. In the case of spermine/NO, cortical perfusion was maintained above the control levels during the ischemic insult. No significant hypotension was elicited by NO donors at the dose-ratios infused. In conclusion, brain damage induced by transient focal ischemia is reduced by intravenous NO donors. Neuroprotective effects of spermine/NO are due at least in part to improvement of brain perfusion, while sodium nitroprusside must provide direct cytoprotection. These results give further support to the protective effect of NO in the early stages of cerebral ischemia and point to the therapeutic potential of NONOates in the management of brain ischemic damage.

We have examined the effects of global ischemia and subsequent reperfusion on the reactivity of goat middle cerebral artery to endothelin-1. The participation of extracellular Ca 2+ in endothelin-1-induced contractions and the ability of the Ca 2+ entry blocker, nicardipine, to counteract them after ischemia were also assessed. Concentration-response curves to endothelin-1 (10 −12 –3×10 −8 mol/L) obtained in arteries from goats subjected to either 5 or 10 minutes of ischemia and 7-day reperfusion did not significantly differ from curves obtained in arteries from sham-operated goats. Concentration-response curves to endothelin-1 in arteries from goats subjected to 20 minutes of ischemia and 7-day reperfusion, however, showed significantly higher pEC 50 (negative logarithm to base 10 of the concentration of endothelin-1 producing 50 of the maximal effects) value ( P max ) values of the concentration-response curves to endothelin-1 were significantly reduced ( P max value was again significantly reduced ( P 2+ -free medium or nicardipine (10 −10 and 10 −8 mol/L), the concentration-response curve to endothelin-1 was significantly inhibited ( P 50 and of E max . In conclusion, there was an increase in the endothelin-1 potency 1 week after 20 minutes of ischemia. At this time, the involvement of dihydropyridine-sensitive L-type Ca 2+ channels in Ca 2+ entry induced by endothelin-1 to develop contraction is reduced when compared with normal arteries. We suggest that the increased reactivity to endothelin-1 could have pathophysiological relevance, and the reduced effect of nicardipine could have therapeutical relevance in cerebral ischemia.

We have analysed the effects of 7,12-O-diacetyl-8-O-benzoil-2,3-diepiingol (DBI), an ingol derivative isolated from E. canariensis, on isometric tension developed by isolated rabbit basilar and carotid arteries. Concentration-response curves to DBI (10−8 - 3 × 10−5 m) were obtained cumulatively in both arteries at resting tension and active tone (KC1, 50 mm). At resting tension, DBI induced a concentration-dependent contraction, which was not inhibited in Ca2+-free medium. H7 (1-(5-isoquinoline sulphonyl)-2-methylpiperazine dichloride) (10−4 m) inhibited the DBI-induced contraction both in basilar and in carotid arteries. Calmidazolium (10−4 m) inhibited the maximum contraction of the carotid artery to DBI, and completely abolished the response in the basilar artery. In pre-contracted basilar arteries DBI induced a concentration-dependent relaxation that was not modified by incubation with NG-nitro-l-arginine (l-NOARG; 10−5 m) or indomethacin (10−5 m). In the carotid artery with active tone DBI induced further contractions, which were not significantly modified by l-NOARG (10−5 m) and were potentiated by indomethacin (10−5 m). These results suggest that DBI contracts rabbit basilar and carotid arteries by a mechanism that is independent of extracellular Ca2+ and involves the participation both of protein kinase C and of calmodulin. DBI relaxes basilar but not carotid arteries by a mechanism independent of the liberation of nitric oxide and prostacyclin. In the carotid artery prostacyclin but not nitric oxide partially counteracts the contractile action of DBI.

Highlights • Voxelwise analysis of structural images is performed in a group of patients with FLE. • Structural abnormalities are found in piriform cortex and adjacent structures including amygdala. • These common areas of structural abnormality are seen independently of the side of seizure focus lateralisation. • This is concordant with previous findings in functional imaging analysis of patients with focal epilepsy., Summary Background Neuronal networks involved in seizure generation, maintenance and spread of epileptic activity comprise cortico-subcortical circuits. Although epileptic foci vary in location across focal epilepsy syndromes, there is evidence for common structures in the epileptogenic networks. We recently reported evidence from functional neuroimaging for a unique area in the piriform cortex, common to focal epilepsies in humans, which might play a role in modulating seizure activity. In this study, we aimed to identify common areas of structural abnormalities in patients with frontal lobe epilepsy (FLE). Methods T1-weighted MRI scans of 43 FLE patients and 25 healthy controls were analysed using voxel based morphometry. Differences in regional grey matter volume were examined across the whole brain, and correlated with age at epilepsy onset, duration and frequency of seizures. Results We detected areas of increased grey matter volume in the piriform cortex, amygdala and parahippocampal gyrus bilaterally, as well as left mid temporal gyrus of patients relative to controls, which did not correlate with any of the clinical variables tested. No common areas of atrophy were detected across the FLE group. Conclusions Structural abnormalities within the piriform cortex and adjacent structures of patients with FLE provide further evidence for the involvement of this area in the epileptogenic network of focal epilepsies. Lack of correlation with duration or age of onset of epilepsy suggests that this area of abnormality is not a consequence of seizure activity.

Se presenta el caso de una paciente recien nacida de termino portadora de un sindrome de Pierre Robin asociada a laringomalacia severa que requirio resolucion quirurgica para estabilizacion de su via aerea superior Se presenta la experiencia clinica en el uso de microdebridador para realizacion de supraglotoplastia como una novedosa alternativa en el tratamiento quirurgico de este tipo de pacientes y se realiza revision de la literatura respecto de esta tecnica.

To assess the impact of medication reconciliation by clinical pharmacist on patient outcomes during transitions of care. In 2012, a Transitional Care team was formed to improve care during the transition of patients from hospital to home. The team consisted of Advanced Practice Registered Nurses, one geriatric certified Registered Nurse, one Master Licensed Social Worker, and one Pharmacist. The pharmacist reviewed hospitalization record of each patient discharged with heart failure, pneumonia, and COPD that met the Transitional Care model criteria. The pharmacist then contacted patients 24 hours after discharge. Medication reconciliation was attempted on all willing participants, medication counseling done and …

This report summarizes the results of a SIM comparison in masss carried out between 7 NMIs. Five mass standards with nominal values 2 kg, 200 g, 50 g, 1 g and 200 mg have been circulated by the NMIs. The results reported by the participants are consistent with each other and with the key comparison reference valu of the comparison CCM.M-K5 to which the present comparison has been linked. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

Diabetes is associated with increased prevalence of hypertension, cardiovascular and renal disease. Atrial natriuretic peptide (ANP) plays an important role in cardiovascular pathophysiology and is claimed to have cardioprotective and renoprotective effect in diabetic patients. The working hypothesis was that alloxan-induced diabetes might modify the vascular effects of ANP in isolated rabbit renal arteries and the mechanisms involved in such actions. Plasma ANP levels were higher in diabetic rabbits than in control rabbits. ANP (10(-12)-10(-7)M) induced a relaxation of precontracted renal arteries, which was lower in diabetic than in control rabbits. In arteries from both groups of animals, endothelium removal decreased the ANP-induced relaxation but inhibition of NO-synthesis did not modify ANP-induced relaxations. In KCl-depolarised arteries, relaxation to ANP was almost abolished both in control and diabetic rabbits. Tetraethylammonium (TEA) partly inhibited the relaxation to ANP in control rabbits but did not modify it in diabetic rabbits. Glibenclamide and 4-aminopyridine inhibited the relaxation to ANP, and these inhibitions were lower in diabetic than in control rabbits. Indomethacin potentiated the relaxation to ANP, more in control than in diabetic rabbits. In the presence of ANP the renal artery released thromboxane A(2) and prostacyclin, and the release of prostacyclin resulted decreased in diabetic rabbits. The present results suggest that diabetes produces hyporeactivity of the rabbit renal artery to ANP by mechanisms that at least include the reduced modulation by prostacyclin and a lower participation of ATP-sensitive K(+) channel (K(ATP)), voltage-sensitive K(+) channels (K(V)) and TEA-sensitive K(+) channels (K(Ca)).

Objective. To determine which intraarticular steroids are used by rheumatologists and whether this use and associated practice vary with time and place of training. Method. American College of Rheumatology members were mailed questionnaires that focused on steroid use in the adult knee. Results. The steroids favored by the respondents were methylprednisolone acetate (MPA), preferred most by those trained in the eastern U.S.; triamcinolone hexacetonide (TH), preferred by those trained in the Midwest and Southwest; and triamcinolone acetonide (TA), preferred by those trained in the West. Only TH was chosen primarily because of efficacy. Regardless of concentration, respondents used 1 ml of steroid. Most (especially those recently trained) combined steroid with local anesthetic. Post-injection instructions varied: 29% did not restrict weight-bearing; 8% recommended limited weight-bearing for 1 week or more. Conclusion. MPA, TH, and TA were favored. Associated techniques varied, based in part on where and when training took place. Research is needed to provide a more rational basis for clinical practice.

This document presents the successful application of pro-active Managed Pressure Drilling (MPD) to drill one section through three different sands; the one in the middle with a low fracture pressure, the lower sand with a formation pressure higher than the frac gradient of the weak formation. The wrong decision to apply MPD in a reactive way leads to NPT, influxes, mud losses and increased risks. It is shown how the conventional procedures to drill and make the trips are replaced by tailored MPD procedures leading to successful results. The Client understands the high value of proactive MPD, not only to drill but also to during trips. The drilling commenced with a MW of 1.6 g/cc and after 100 m the MW was increased to 1.62 g/cc (it is a routine procedure in the field to increase the mud density prior to reaching the expected high pressure zones while drilling conventionally). Some meters after start drilling the low frac gradient sand total mud losses were observed. The MW was reduced from 1.62 to 1.52 g/cc and MPD was implemented in a proactive manner whereby the BHP was maintained constant. The big challenge was to control the well at all times avoiding a catastrophic condition.

Leptin and adiponectin are cytokines produced by adipose tissue with opposite effects on tumor growth: the former stimulate whereas the latter inhibit it. The objective was to analyze the association of LEP A19G and ADIPOQ+45 T/G and +276 G/T polymorphisms in Mexican patients with colorectal cancer (CRC). 68 unrelated patients with CRC (study group) and 102 blood donors (control group); all subjects were Mestizos from western Mexico. The polymorphisms were established by PCR-RFLP on DNA samples obtained from peripheral blood. The LEP A19G polymorphism showed significant differences between CRC patients and control group (p= 0.01 for G/A genotype and p= 0.02 for the recessive model G/G +G/A); yet, in the analysis stratified by gender, this difference remained significant only in males. The ADIPOQ polymorphisms did not shown any significant differences. Our results suggest that the A19G LEP polymorphism is associated with CRC in Mexican patients.

Fluorimetric determinations of aluminium and gallium, based on the formation of fluorescence complexes between Al(III) or Ga(III) and salicylaldehyde-1-phthalazinohydrazone, SAPhH, are proposed. The Al(III)-SAPhH complex exhibits fluorescence with maximum emission at 475 nm when excited at 414 nm; the Ga(III)-SAPhH chelate has emission and excitation maxima at 480 and 410 nm, respectively. For both determinations the range of application is 10–100 ng/ml. Aluminium has been determined in waters, and gallium in aluminium and nickel alloys.

Cardiovascular disease is the major cause of morbidity and mortality in diabetic patients, which in turn is also associated with low levels of serum testosterone. The working hypothesis was that diabetes might modify the mechanisms involved in the vascular actions of testosterone in isolated rabbit carotid arteries. Testosterone (10 −8 –3 × 10 −4 M) induced a concentration-dependent relaxation of precontracted carotid arteries, which was higher in diabetic than in control rabbits. In control rabbits neither endothelium removal nor the nitric oxide synthase (NOS) inhibitor N G -nitro- l -arginine ( l -NOArg, 10 −5 M) modified the relaxant action of testosterone, and the cyclooxygenase (COX) inhibitor indomethacin (10 −5 M) enhanced this relaxation. In contrast, in diabetic rabbits endothelium removal, l -NOArg (10 −5 M) or indomethacin (10 −5 M) inhibited the testosterone induced relaxation. In arteries from diabetic rabbits, eNOS, iNOS and COX-2 expression and testosterone induced release of prostacyclin resulted enhanced in comparison with arteries from control rabbits. Testosterone (10 −4 M) strongly inhibited CaCl 2 (10 −5 –3 × 10 −2 M) concentration-related contractions of the carotid artery both in control and diabetic rabbits. These results suggest that testosterone relaxes the rabbit carotid artery by blocking the extracellular calcium entry. Diabetes enhances the vasodilator response of the rabbit carotid artery to testosterone by a mechanism that at least includes an increased modulatory activity of the endothelial nitric oxide and an augmented release of COX-2 vasodilator, prostacyclin rather than the absence of COX-1 vasoconstrictor, thromboxane A 2 . The hypotestosteronemia observed in diabetic rabbits could be a consequence of the increased expression of iNOS and could contribute to the hyperreactivity of the rabbit carotid artery to testosterone.

The temperature dependence of the differential resistance by area product at zero bias (R0 A) of boron‐implanted n‐on‐p infrared photodiodes made in x≊0.20 Hg1−xCdxTe has been measured and characterized as a function of the implanted dose assuming a simple model of the junction. The R0 A product and its functional dependence in the different temperature ranges are found to be dependent on the implanted dose in n+p as‐implanted abrupt junctions. The best performance diodes are found at the lowest implanted dose. The results indicate that there is an upper limit of the R0 A, in the range where the current is controlled by a minority‐carrier diffusion mechanism, that is determined in n+p junctions by the p‐side contribution. However, the indicated behavior of R0 A and its functional dependence at low temperatures supports the hypothesis defended by some workers in the literature indicating that the n‐side contribution to the current‐voltage characteristics may be important under some conditions, such as is t...

The electric effects of implantation of boron into p-type MZT (mercury zinc telluride) has been evaluated using Hall effect data. The data show that boron implantation, without damage annealing, produces an n-type layer in MZT. This behavior appears to be related to implantation damage as this also happens in other II–VI compounds, such as MCT (mercury cadmium telluride). In MZT, a freeze-out of majority carriers is observed in the implanted layer with a characteristic activation energy E A ≈ 10 meV. This effect has not been found in MCT.

DNA recognition by antibodies is a key feature of autoimmune diseases, yet model systems with structural information are very limited. The monoclonal antibody ED-10 recognizes one of the strands of the DNA duplex used in the immunogenic complex. Modifications of the 5′ end decrease the binding affinity and short oligonucleotides retain high binding affinity. We determined crystal structures for the Fab bound to a 6-mer oligonucleotide containing the specific sequence that raised the antibody and compared it with the unliganded Fab. Only the first two bases from the 5′ end (dTdC) display electron density and we observe four key hydrogen bonds at the interface. The thymine ring is stacked between TrpH50 and TrpH95, and the cytosine ring is packed against TyrL32. Upon DNA binding, TyrH97 and TrpH95 rearrange to allow subnanomolar binding affinity, five orders of magnitude higher than other reported complexes, possibly because of having gone through affinity maturation. This structure represents the first bona fide antibody DNA immunogen complex described in atomic detail. Fil: Sanguineti, Santiago. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Centeno Crowley, Juan M.. Fundación Instituto Leloir; Argentina Fil: Lodeiro, Anibal. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Cerutti, Maria Laura. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Goldbaum, Fernando Alberto. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Wilson, Ian A.. The Scripps Research Institute; Estados Unidos Fil: Stanfield, Robyn L.. The Scripps Research Institute; Estados Unidos Fil: de Prat Gay, Gonzalo. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

Purpose: In 1998, four cases of contaminated allografts for anterior cruciate ligament (ACL) reconstruction resulted in Clostridium infection, and a patient with Clostridium infection from a femoral condylar allograft died. It was subsequently published that implanting surgeons should culture ACL allografts so that action could be taken should highly pathogenic bacteria be encountered. The purpose of this study is to test the hypothesis that ACL allograft cultures correlate with clinical infections. Methods: Since October 2003, a single surgeon performing ACL reconstruction prospectively cultured all allografts in the operating room before implantation. After culture, grafts were thawed in warm saline mixed with bacitracin. All patients received a single dose of preoperative antibiotics. Final culture results were obtained in all patients, and all patients were followed for a minimum of 90 days to evaluate for postoperative infection. The cost of cultures was determined by multiplying hospital charges by the hospital cost-to-charges ratio. Results: Two hundred and ten cases were included. Ten allografts (4.8%) had positive culture results (6 coagulase-negative Staphylococci, 1 alpha- Streptococcus -not-group-B, 1 Enterobacter , 1 Clostridium , and 1 polymicrobial [ Klebsiella , Escherichia coli , and Enterococcus ]). None of these patients had signs of infection; the three positive highly pathogenic bacteria ( Enterobacter , Clostridium , and polymicrobial) graft recipients were treated with antibiotics. The others were observed. One patient with negative cultures developed Staphylococcus aureus infection. Mean culture cost was $127 (USD). Conclusions: Our results demonstrate that ACL allograft cultures do not correlate with clinical infections. Level of Evidence: Level I, diagnostic study (testing of previously developed diagnostic criteria [culture]) in a series of consecutive patients (with universally applied reference gold standard [clinical evaluation for knee sepsis]).

Influenza is a major cause of respiratory tract illness in infants. The clinical characteristics of these infections are non-specific and the burden of influenza is frequently underestimated in very young children. The objective of this study was to describe confirmed influenza infections in infants2 years attended in a level II public hospital. A second-rate aim was to compare influenza infections in hospitalized infants with respiratory syncytial virus (VRS) infection in the same population.We performed a descriptive, prospective study between 1991 and 2003 in infants younger than 24 months of age, who were admitted to the Severo Ochoa Hospital (Leganés. Madrid) with fever or respiratory tract infection. Virological diagnosis was made with direct immunofluorescent assay and/or reverse transcription-polymerase chain reaction on specimens obtained from nasopharyngeal washings. The patients' clinical characteristics were recorded. Patients with influenza infection were compared with a similar group of infants with RSV infection.We analyzed hospitalized 100 infants with influenza infection. Influenza caused 4.1% of the admissions in infants with fever or respiratory tract infection. Influenza A was isolated in 83%, influenza B in 12% and influenza C in 5% of the patients. The mean age of hospitalized infants was 8.3 +/- 5.9 months and the most frequent clinical diagnoses were bronchiolitis in 38%, recurrent wheezing in 25%, upper respiratory tract infection in 19% and pneumonia in 9%. Fever38 degrees C was present in 83% of the patients. Radiologic infiltrate was found in 65% of the children. Oxygen saturation less then 95% was present in 44%. In children under 6 months of age fever was less frequent (p = 0.049) and upper respiratory tract infection was more frequent (p = 0.01). Patients with influenza virus infection were older (p = 0.002), more frequently presented fever (p0.0001) and radiologic infiltrate (p0.001) than infants with RSV infection. Bronchiolitis was more frequent in the RSV group (p = 0.006).Influenza infection is a major cause of respiratory tract disease in hospitalized infants. It is an etiologic cause of bronchiolitis, recurrent wheezing, and fever and radiologic consolidations are frequent. Clinical presentation is milder in children under 6 month of age. The characteristics of influenza infection differ substantially from those of RSV infection.

Despite the fact that E7 is a major transforming oncoprotein in papillomavirus, its structure and precise molecular mechanism of action remain puzzling to date. E7 proteins share sequence homology and proteasome targeting properties of tumor suppressors with adenovirus E1A and SV40 T antigen, two other paradigmatic oncoproteins from DNA tumor viruses. High-risk HPV16 E7, a nonglobular dimer with some properties of intrinsically disordered proteins, is capable of undergoing pH-dependent conformational transitions that expose hydrophobic surfaces to the solvent. We found that treatment with a chelating agent produced a protein that can readily assemble into homogeneous spherical particles with an average molecular mass of 790 kDa and a diameter of 50 nm, as determined from dynamic light scattering and electron microscopy. The protein undergoes a substantial conformational transition from coil to beta-sheet structure, with concomitant consolidation of tertiary structure as judged by circular dichroism and fluorescence. The assembly process is very slow, in agreement with a substantial energy barrier caused by structural rearrangements. The resulting particles are highly stable, cooperatively folded, and capable of binding both Congo Red and thioflavin T, reporters of repetitive beta-sheet structures similar to those found in amyloids, although no fibrillar or insoluble material was observed under our experimental conditions. Fil: Alonso, Leonardo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Garciaa Alai, Maria M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Smal, Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Centeno, Juan M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Iacono, Ruben Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Castaño, Eduardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Gualfetti, Peter. Genencor International; Estados Unidos Fil: de Prat Gay, Gonzalo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina

Anti-double-stranded DNA monoclonal antibodies against a viral transcriptional regulatory site are capable of discriminating single-base replacements with affinities of 1 x 10(-9) M, which were optimized for the length of the duplex used as the immunogen. Their affinity for DNA duplexes of increasing length is lower, but reaches a plateau at 2 x 10(-8) M, still a fairly high affinity compared to those of most known natural anti-DNA antibodies. The ability of the antibodies to bind to a 166 bp DNA fragment containing the specific sequence strongly suggests that these have the potential of binding the specific sequence within larger genomic DNA fragments. Electrostatic interactions do not play a significant role, the opposite of what is observed in natural DNA binding interfaces. In addition, the insensitivity of the antibody-DNA interaction to solute effects is indicative of a marginal participation of water molecules at the interface compared to the level of participation at the natural E2-DNA interface. Spectroscopic evidence of base unstacking strongly suggests substantial denaturation of antibody-bound DNA, in agreement with thermodynamic results that show an unusual positive heat capacity change, which could be explained at least in part by the exposure of DNA bases upon binding. Lower local DNA stability cooperates with sequence recognition in producing the highest binding affinity. A slow rate of antibody-DNA association indicates an energy barrier imposed by conformational rearrangements, as opposed to an electrostatically assisted diffusion-controlled collision in the E2 DNA binding domain. While the E2-DNA interaction takes place through a typical direct readout mechanism, the anti-double-stranded DNA monoclonal antibody-DNA interaction could be viewed as a distinctive case of indirect readout with a significant distortion in the DNA conformation. However, the precise mechanism with which the DNA bases are accommodated in the antibody combining site will require structural analysis at atomic resolution. These results constitute a first stage for unveiling the unusual molecular recognition mechanism of a specific DNA sequence by antibodies. This mechanism could represent the strategy with which the immune system tightly and specifically recognizes a DNA antigen. Fil: Di Pietro, Santiago M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Centeno, Juan M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Cerutti, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Lodeiro, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Ferreiro, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Alonso, Leonardo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Schwarz, Frederick P.. National Institute of Standards and Technology; Estados Unidos Fil: Goldbaum, Fernando Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: de Prat Gay, Gonzalo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina

The E2 transcriptional activator of the human papillomavirus regulates the expression of most viral transcripts. Its binding to specific target DNA sequences involves large conformational changes in the interacting macromolecules. The high stability of the E2:DNA complex prompted us to analyze the role of macromolecular interactions and adjuvant emulsions in the appearance of conformation-specific antibodies. We demonstrate that immunization with free or DNA-complexed E2 emulsified in an oil-in-water adjuvant elicits a humoral response shifted to the recognition of discontinuous epitopes. Epitope mapping and functional analysis of the generated anti-E2 mAbs reveals that two separate antibodies populations can be obtained: those able to form a stable ternary complex with protein and DNA, and those which recognize the DNA-binding surface of the transcription factor, interfering with E2 binding to DNA. Fil: Cerutti, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Centeno, Juan M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: de Prat Gay, Gonzalo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Goldbaum, Fernando Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina

Desde la revolución “flexneriana” de hace 100 años hubo muchos intentos de cambios en la enseñanza de la medicina y surgieron nuevas tendencias generales en educación médica.Principalmente surge la necesidad de superar el modelo biomédico clásico hacia uno más centrado en la persona (y en la sociedad). El curriculum tiende a ser más competo e integral, con la incorporación de aspectos comunitarios, de integración de dimensiones clínicas y de habilidades interpersonales. La planificación curricular se adapta mejor a las necesidades del estudiante y de la sociedad.La admisión de los estudiantes y su selección, busca hacerse más inclusiva, equitativa, y basada en la ciencia de la evaluación.Aparecen modelos de universidades virtuales que seguramente en el futuro serán exitosas, a partir del rápido desarrollo de simuladores, de nuevas tecnologías de la información y del uso de redes sociales. Hay muchos ejemplos de modelos mixtos de aprendizaje a distancia y actividades presenciales (blendede-learning).Se incorpora la concepción de entrenamiento y formación multiprofesional e interprofesional, e incluso la integración de la formación de pregrado y de posgrado en algunas escuelas de acuerdo a la orientación elegida.La evaluación de los saberes y las competencias profesionales tienden a hacerse cada vez más descriptivas, con énfasis en la reflexión y en las habilidades metacognitivas, y utilizan tests sofisticados (OSCE, miniCEX, Script Concordance Tests).La formación docente tiende a ser más longitudinal, reflexiva, interactiva y favoreciendo el compromiso personal y profesional como elemento de aprendizaje.En definitiva muchos aspectos de la educación médica está cambiando y las nuevas tendencias se van imponiendo como un medio de adaptarse a las nuevas realidades sociales. ABSTRACTSome actual trends in Medical Education. Since the “Flexneriane” revolution 100 years ago, many attempts have been made to change how medicine is taught, and many new general tendencies in education have appeared.Principally the necessity to surpass the classic biomedical model with one more focussed on the individual and society has become evident. The curriculum tends to be more comprehensive with the inclusion of community needs, integration different clinical dimensions and interpersonal skills.The selection and admission of students into medical schools seeks to be more inclusive, equalising and based on the science of evaluation.Models of virtual universities have been emerging which will surely be successful in the future. They are based on the constant development of simulators, new information technology and the use of social media networks. There are many examples of mixed models of distance learning and blended e-learning .The concept of multi-professional and inter-professional practice and training including undergraduate and postgraduate training in some schools according to selected orientation has been incorporated.Evaluation of knowledge and professional skills tends to be more descriptive, with an emphasis on reflection and on metacognitive skills as well as the use of sophisticated tests such as OSCE, miniCEX, and Script Concordance tests.Educational training has become longitudinal, reflexive, interactive and encourages personal and professional commitment as an element for learning.Many aspects of medical education are definitely changing and these new tendencies are a medium through which one can adapt to the new social realities.

Mentoring plays a central role in academic life. It is based mainly on mutual respect between mentor and mentee, and requires effort, continuity and consideration for different learning styles. It demands hard work, discipline, rigour, creativity, honesty and integrity. Both mentor and mentee must profit and learn from the process of mentoring in order to fulfil an essential purpose of the university. Their relationship represents the bond between the past and the future.

Estrogens could play a cardiovascular protective role not only by means of systemic effects but also by means of direct effects on vascular structure and function. We have studied the acute effects and mechanisms of action of 17-beta-estradiol on vascular tone of rabbit isolated carotid artery. 17-Beta-estradiol (10, 30, and 100 microM) elicited concentration-dependent relaxation of 50 mM KCl-induced active tone in male and female rabbit carotid artery. The stereoisomer 17-alpha-estradiol showed lesser relaxant effects in male rabbits. Endothelium removal did not modify relaxation induced by 17-beta-estradiol. The NO synthase inhibitor L-NAME (100 microM) only reduced significantly relaxation produced by 30 microM 17-beta-estradiol. Relaxation was not modified by the estrogen receptor antagonist ICI 182,780 (1 microM), the protein synthesis inhibitor cycloheximide (1 microM), and the selective K(+) channel blockers charybdotoxin (0.1 microM) and glibenclamide (1 microM). CaCl(2) (30 microM -10 mM) induced concentration-dependent contraction in rabbit carotid artery depolarized by 50 mM KCl in Ca(2+) free medium. Preincubation with 17-beta-estradiol (3, 10, 30, or 100 microM) or the L-type Ca(2+) channel blocker nicardipine (0.01, 0.1, 1, or 10 nM) produced concentration-dependent inhibition of CaCl(2)-induced contraction. In conclusion, 17-beta-estradiol induces endothelium-independent relaxation of rabbit carotid artery, which is not mediated by classic estrogen receptor and protein synthesis activation. The relaxant effect is due to inhibition of extracellular Ca(2+) influx to vascular smooth muscle, but activation of K(+) efflux is not involved. Relatively high pharmacological concentrations of estrogen causing relaxation preclude acute vasoactive effects of plasma levels in the carotid circulation.

The influence of diabetes on the response of isolated rabbit renal arteries to 5-hydroxytryptamine (5-HT) was examined. 5-HT induced a concentration-related contraction that was higher in arteries from diabetic rabbits than in arteries from control rabbits. Endothelium removal did not significantly modify 5-HT contractions in arteries from control rabbits but enhanced the response to 5-HT in arteries from diabetic rabbits. Incubation with N G -nitro- l -arginine ( l -NA) enhanced contractions to 5-HT in arteries from control and diabetic rabbits. In arteries with endothelium, this l -NA enhancement was lower in diabetic rabbits than in control rabbits. In arteries without endothelium, incubation with l -NA enhanced the maximal contractions to 5-HT in control rabbits but did not in diabetic rabbits. Indomethacin inhibited 5-HT-induced contraction of arteries from control rabbits and enhanced the maximal contraction to 5-HT of arteries from diabetic rabbits. In summary, diabetes enhances contractile response of rabbit renal artery to 5-HT. In control animals, this response is regulated by both endothelial and non-endothelial (neuronal) nitric oxide (NO) and by a vasoconstrictor prostanoid. Diabetes impairs the release of non-endothelial NO and the vasoconstrictor prostanoid.

Two techniques of sperm concentration (centrifugation or filtering) and sperm separation technique with glass wool were applied to the sperm samples collected from 3 pony stallions (6 ejaculates; 2 from each stallion). Ejaculates were extended to a final concentration of 50 × 106 spermatozoa mL–1 using a nonfat dry milk-based extender and evaluations occurred at 24, 48, and 72 h after immediate ejaculate dilution and cooling. Each stallion was considered as a block, and semen from each stallion was assigned to 4 treatments: Group A (control): extended semen alone; Group B: extended-centrifuged semen; Group C: extended-sperm filtered semen; Group D: extended-glass wool-separated semen. All groups were tested for pH, osmolarity, motility, morphology, membrane functionality (hyposmotic), and cell viability (MTT assay). The experimental design was performed using a split-plot model. Data analysis at the level of 5% was performed using ANOVA and Bonferroni as post-hoc test. Data are presented as mean ± standard error. Group D had the highest rate of viable cells (P

Resumo não disponivel.

Resumo não disponível.

The role of gene induction (expression of HSP72 and c-JUN proteins) and delayed ischemic cell death (in situ labeling of DNA fragmentation) have been investigated in the goat hippocampus after transient global cerebral ischemia. The animals were subjected to 20-min ischemia (bilateral occlusion of the external carotid arteries plus bilateral jugular vein compression) and allowed to reperfuse for 2 h, and then 1, 3, and 7 days. Histological signs of cell loss were not found in the hippocampus at 2 h, 1 day, or 3 days of reperfusion. However, such an ischemic insult produced extensive, selective, and delayed degeneration in the hippocampus, as 68% of the neurons in CA1 had died at 7 days, but cell loss was not detected in CA3 and dentate gyrus fields. Concomitantly, a high percentage of TUNEL-positive CA1 neurons (60+/-9%, mean +/- SEM) was seen at 7 days, but not at the earlier time points. Mild induction of HSP72 was detected in the goat hippocampus after ischemia. The maximum percentage of HSP72-positive neurons (10-15%) was shown at 3 days of reperfusion and was concentrated mainly in the CA3 field, subiculum, and hilus, rather than in the CA1 field, whereas HSP72 expression was hardly detected at 7 days. At this later time point, scattered induction of nuclear c-JUN was found in a few neurons. The results show that: 1) postischemic delayed neuronal death selectively affects the CA1 field in the goat hippocampus, a phenomenon which seems to take longer to develop than in previously reported rodent models; and 2) postischemic expression of c-JUN does not appear to be related to cell death or survival, while the inability of most CA1 neurons to express HSP72 could contribute to neuronal death.