Telmisartán y losartán: las marcadas diferencias entre sus propiedades químicas y farmacológicas pueden explicar la diferencia en la eficacia terapéutica en pacientes hospitalizados con covid-19 / Telmisartan and losartan: marked differences in chemical and pharmacological properties may explain differences in therapeutic efficacy in hospitalized patients with COVID-19

El objetivo de este artículo es comparar las propiedades químicas y farmacológicas del telmisartán y el losartán, y su metabolito activo EXP3174, con el fin de entender por qué el telmisartán es efectivo en pacientes hospitalizados con Covid-19 mientras que el losartán no lo es. Se llevó a cabo una revisión bibliográfica exhaustiva de las propiedades químicas, farmacocinéticas y farmacodinámicas de ambos fármacos y se destacaron las diferencias más importantes que podrían estar relacionadas con su efectividad en pacientes con Covid-19. Se concluyó que las propiedades farmacológicas del telmisartán, como su mayor afinidad por el receptor AT1, su duración de acción prolongada y su capacidad para modular la inflamación podrían explicar su efectividad en pacientes con Covid-19. Por otro lado, las propiedades farmacológicas del losartán, como su menor afinidad por el receptor AT1 y su rápido metabolismo, pueden limitar su efectividad en pacientes con Covid-19. Estos resultados resaltan la importancia de comprender las propiedades químicas y farmacológicas de los medicamentos para identificar posibles candidatos terapéuticos efectivos en el tratamiento de Covid-19. (AU)

The objective of this article is to compare the chemical and pharmacological properties of telmisartan and losartan and their active metabolite EXP3174 to understand why telmisartan is effective in hospitalized patients with COVID-19 while losartan is not. A comprehensive literature review of the chemical, pharmacokinetic and pharmacodynamic properties of both drugs was done to highlight the most important differences that may be related to their efficacy in patients with COVID-19. It was concluded that the pharmacological properties of telmisartan, such as its higher affinity for the AT1 receptor, its long duration of action and its ability to modulate inflammation, could explain its efficacy in patients with COVID-19. On the other hand, the pharmacological properties of losartan, such as its lower affinity for the AT1 receptor and its rapid metabolism, may limit its efficacy in patients with COVID-19. These results highlight the importance of understanding the chemical and pharmacological properties of drugs to identify potential effective therapeutic candidates for the treatment of COVID-19. (AU)

La inflamación como el nexo entre la enfermedad periodontal y la enfermedad cardiovascular / Inflammation as a link between periodontal disease and cardiovascular disease

La periodontitis es una enfermedad no transmisible, con una alta prevalencia, que oscila entre el 45% y el 50% de la población mundial, ocupando el sexto lugar entre las enfermedades más frecuentes de la huma-nidad. Existe suficiente evidencia que avala la relación entre la enfermedad periodontal y la enfermedad car-diovascular, responsable de aproximadamente el 45% de las muertes en países desarrollados, compren-diendo en su causalidad al infarto de miocardio, el accidente cerebrovascular, la insuficiencia cardíaca y las arritmias, que causan alrededor del 95 % de las muertes relacionadas con la enfermedad cardiovas-cular. Ambas patologías presentan factores de riesgo comunes ampliamente reconocidos, como la diabetes y el tabaquismo, pero además manifiestan caracte-rísticas genéticas y epigenéticas que avalan distintos mecanismos etiopatológicos. Más allá de los factores de riesgo comunes, se han propuesto dos mecanis-mos para explicar la relación entre la enfermedad periodontal y las cardiovasculares. Uno de ellos, constituye la invasión directa de patógenos periodontales en las células endoteliales. El otro mecanismo sugerido (vía indirecta), ocasionado por la respuesta inflamatoria sistémica que resulta en niveles cróni-camente elevados de diferentes citoquinas, también relacionadas con la enfermedad vascular aterosclerotica como IL-1ß, IL-6, IL-8, TNF-α, PCR y la proteína quimioatrayente de monocitos, podría estar mediado por productos bacterianos, como los lipopolisacári-dos que alcanzarían la circulación induciendo una potente respuesta inmunitaria. Estos mecanismos pueden actuar inflamando las células endoteliales, modulando el metabolismo de los lípidos y aumentan-do el estrés oxidativo, favoreciendo la aterosclerosis, conformando la expresión de un fenotipo arterial in-flamatorio, generando el nexo entre la enfermedad periodontal y las patologías cardiovasculares (AU))

Periodontitis is a non-communicable disease which is highly prevalent worldwide. It was reported to range from 45% to 50% around the world and it was the sixth most prevalent condition of humanity. Consistent body of evidence explains the relationship between periodontal disease and other common systemic conditions such as cardiovascular disease. Periodontitis is likely to cause a 45% of deaths in developed countries, including myocardial infarction, stroke, heart failure and arrhythmias that cause about a 95% of deaths related to cardiovascular disease.Both diseases share many risk factors, such as diabetes and smoking; but also, genetic, and epigenetic characteristics support several etiopathological mechanisms. Beyond the common risk factors, two mechanisms have been proposed to elucidate the relationship between the periodontal disease and cardiovascular diseases. One of them supports the concept that periodontal pathogens are capable of the direct invasion of endothelial cells. The other mechanism suggested (indirect pathway), caused by the disease resulting in chronically elevation of CRP, inflammatory cytokines, the monocyte chemoattractant protein, could be mediated by bacterial products, such as lipopolysaccharides, wich induce a potent immune response and can accelerate endothelial dysfunction. These mechanisms may act by inflaming endothelial cells, modulating lipid metabolism and increasing oxidative stress, favoring atherosclerosis, determining the expression of an inflammatory arterial phenotype, generating the link between periodontal disease and cardiovascular pathologies (AU)

Telmisartan for treatment of Covid-19 patients: An open multicenter randomized clinical trial.

Background: Angiotensin receptor blockers (ARBs), such as telmisartan, have been postulated to treat Covid-19-induced lung inflammation. Methods: This is a parallel-group, randomized, two-arm, open-label, adaptive, multicenter superiority trial with 1:1 allocation ratio. Participants included patients from 18 years of age hospitalized with Covid-19 with 4 or fewer days since symptom onset enrolled at a university and a community hospital in Buenos Aires, Argentina. Exclusion criteria included prior intensive care unit (ICU) admission and use of ARBs/angiotensin converting enzyme inhibitors at randomization. Control arm received standard care alone and treatment arm telmisartan 80 mg twice daily for 14 days. Primary outcomes were C-reactive protein (CRP) plasma levels at day 5 and 8 after randomization. Secondary outcomes included time to discharge within 15 days, admission to ICU and death at 15- and 30-days. NCT04355936 (Completed). Findings: A pragmatic decision to end the study before the third interim analysis was made on Oct. 30th due to sharp reduction in recruitment. A total of 162 patients were randomized. 158 patients enrolled between May 14 and October 30 2020, were included in the analysis, 80 in the standard care and 78 in the telmisartan added to standard care group. Baseline absolute CRP serum levels were 5.53 ± 6.19 mg/dL (95% CI 6.91 to 4.15, n = 80) and 9.04 ± 7.69 (95% CI 9.04 to 10.82, n = 74) in the standard care and telmisartan added to standard care groups, respectively. Day 5 control-group CRP levels were 6.06 ± 6.95 mg/dL (95% CI 7.79-4.35, n = 66) while telmisartan group were 3.83 ± 5.08 mg/dL (95% CI 5.08-2.59, n = 66, p = 0.038). Day 8 CRP levels were 6.30 ± 8.19 mg/dL (95% CI 8.79-3.81, n = 44) and 2.37 ± 3.47 mg/dL (95% CI 3.44-1.30, n = 43, p = 0.0098) in the control and telmisartan groups, respectively (all values expressed as mean ± SD). Kaplan-Meier analysis showed that telmisartan-treated patients had a lower median time-to-discharge (control=15 days; telmisartan=9 days). Death by day 30 was reduced in the telmisartan-treated group (control 22.54%, 16/71; telmisartan 4.29%, 3/70 participants; p = 0.0023). Composite ICU, mechanical ventilation or death was reduced by telmisartan treatment at days 15 and 30. No adverse events were reported. Interpretation: Our study suggests that the ARB telmisartan, a widely used antihypertensive drug, is safe and could reduce morbidity and mortality in hospitalized patients infected with SARS -CoV-2 by anti-inflammatory effects. Further studies employing telmisartan are needed for confirmation of our results and to define its true therapeutic value as a tool against Covid-19.

Angiotensin Receptor Blockers for COVID-19: Pathophysiological and Pharmacological Considerations About Ongoing and Future Prospective Clinical Trials.

COVID-19 pandemic demands a swift response to find therapeutic tools that effectively reduce morbidity and mortality. Despite initial fears, evidence from retrospective observational studies supports the inhibition of the renin-angiotensin system as an emerging pathway to delay or moderate angiotensin II-driven lung inflammation. This has triggered several prospective clinical trials. In this commentary we provide an overview and analysis of current ongoing clinical trials aimed at evaluating the therapeutic efficacy of angiotensin receptor blocker (ARB) use in COVID-19. The relevance of the results of these trials will have to be interpreted depending on the stage and severity of the disease and in light of the start time of their prescription related to the time of diagnosis of COVID-19 as well as the administered doses.

Continuation versus discontinuation of renin-angiotensin system inhibitors in patients admitted to hospital with COVID-19: a prospective, randomised, open-label trial.

BACKGROUND: Biological considerations suggest that renin-angiotensin system inhibitors might influence the severity of COVID-19. We aimed to evaluate whether continuing versus discontinuing renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) affects outcomes in patients admitted to hospital with COVID-19. METHODS: The REPLACE COVID trial was a prospective, randomised, open-label trial done at 20 large referral hospitals in seven countries worldwide. Eligible participants were aged 18 years and older who were admitted to hospital with COVID-19 and were receiving a renin-angiotensin system inhibitor before admission. Individuals with contraindications to continuation or discontinuation of renin-angiotensin system inhibitor therapy were excluded. Participants were randomly assigned (1:1) to continuation or discontinuation of their renin-angiotensin system inhibitor using permuted block randomisation, with allocation concealed using a secure web-based randomisation system. The primary outcome was a global rank score in which participants were ranked across four hierarchical tiers incorporating time to death, duration of mechanical ventilation, time on renal replacement or vasopressor therapy, and multiorgan dysfunction during the hospitalisation. Primary analyses were done in the intention-to-treat population. The REPLACE COVID trial is registered with ClinicalTrials.gov, NCT04338009. FINDINGS: Between March 31 and Aug 20, 2020, 152 participants were enrolled and randomly assigned to either continue or discontinue renin-angiotensin system inhibitor therapy (continuation group n=75; discontinuation group n=77). Mean age of participants was 62 years (SD 12), 68 (45%) were female, mean body-mass index was 33 kg/m2 (SD 8), and 79 (52%) had diabetes. Compared with discontinuation of renin-angiotensin system inhibitors, continuation had no effect on the global rank score (median rank 73 [IQR 40-110] for continuation vs 81 [38-117] for discontinuation; ß-coefficient 8 [95% CI -13 to 29]). There were 16 (21%) of 75 participants in the continuation arm versus 14 (18%) of 77 in the discontinuation arm who required intensive care unit admission or invasive mechanical ventilation, and 11 (15%) of 75 participants in the continuation group versus ten (13%) of 77 in the discontinuation group died. 29 (39%) participants in the continuation group and 28 (36%) participants in the discontinuation group had at least one adverse event (χ2 test of adverse events between treatment groups p=0·77). There was no difference in blood pressure, serum potassium, or creatinine during follow-up across the two groups. INTERPRETATION: Consistent with international society recommendations, renin-angiotensin system inhibitors can be safely continued in patients admitted to hospital with COVID-19. FUNDING: REPLACE COVID Investigators, REPLACE COVID Trial Social Fundraising Campaign, and FastGrants.

Cognitive impairment related to arterial stiffness in cardiovascular disease patients with severe periodontitis / Deterioro cognitivo relacionado a la rigidez arterial en pacientes con enfermedad cardiovascular y periodontitis grave

ABSTRACT Severe periodontal disease (SPD) associated with systemic peripheral inflammation, cognitive impairment (CI) and arterial stiffness (AS) has been recognized. The aim of this study was to investigate whether CI and arterial stiffness (AS) occur in cardiovascular disease (CVD) patients with SPD. A crosssectional case-control study included hospitalized patients with CVD. Demographic characteristics, CVD and atherogenic risk factors were recorded. SPD was diagnosed by clinical and radiographic dental examinations. Dental clinical attachment level (CAL) and CAL % were recorded. A Mini-Mental State Examination test (MMSE) assessed cognition, a MMSE score of < 27 was set as the cut-off point of CI; a score > 27 was considered as no CI. Patients were categorized into: MMSE<27 (cases) and MMSE>27 (controls). AS was evaluated by pulse wave velocity (PWV). Serum VCAM-1 levels were determined in a random sample. Results: This study comprised 91 patients (cases, n=26; 29.6%; controls, n=65, 71.4%); aged 73±8 vs. 73±7 years, respectively (p=0.73), of whom 53.8% and 36.9% respectively, were women; SPD was found to be a risk factor for CI; the presence of SPD increased the risk for MMSE <27 by an average 5.39 times (model 1). PWV was associated with MMSE < 27 in the three models. The risk of having MMSE < 27 increased an average of2.404-fold for each 1-unit increase in PWV SPD and AS had significant and independent associations on the risk for development CI. MMSE negatively correlated with CAL% (r=0.69) and PWV (r=0.70). PWV positively correlated with CAL% (r=0.67). Serum VCAM-1 levels were higher in SPD with lower MMSE scores. In conclusion, SPD increases the risk of development of cognitive decline in CVD patients. PWV was directly associated with the risk of cognitive decline. These findings denote a significant opportunity to improve periodontal health in order to avert CI in CVD patients.

RESUMEN La enfermedad periodontal severa (EPS) podría estar asociada a la rigidez arterial (RA) y al deterioro cognitivo (DC). Se realizó un estudio transversal de casos y controles y se investigó la presencia de RA y DC en pacientes con enfermedad cardiovascular (ECV) y EPS. En pacientes hospitalizados con ECVse registraron las características demográficas y factores de riesgo aterogénicos. El DC se diagnosticó a través del Mini-Mental State Examination (MMSE). Punto de corte: MMSE<27 (casos); puntaje >27 ausencia de DC (controles). La EPS fue diagnosticada clínica y radiográficamente. Se registraron el nivel inserción clínica (NIC) y NIC %. La RA fue evaluada a través de la velocidad de onda de pulso (VOP). VCAM-1 sérico se determinó en una muestra aleatoria. Se incluyeron 91 pacientes (casos,n=26; 29.6%; controles,n=65, 71.4%); edad promedio: 73±8 vs. 73±7 años, respectivamente (p=0.73); % de mujeres: 53.8 vs. 36.9, respectivamente y EPS (n=54) y ausencia de EP (noEP) en 37. MMSE< 27 en 26 pacientes; 23 de ellos, con EPS. La presencia de EPS aumentó el riesgo de MMSE< 27 en 5.39 veces (modelo 1). La VOP se asoció a MMSE< 27 (Modelo 1, 2 y 3). El riesgo de MMSE< 27 incrementó en promedio en 2.40 veces por cada aumento de unidad de VOP. EPS y RA mostraron asociaciones significativas e independientes sobre el riesgo de DC. MMSE se correlacionó negativamente con NIC % (r=0.69) y POV (r=0.70); y POV, positivamente con NIC % (r=0.67). Los niveles séricos de VCAM-1 fueron más elevados en presencia de EPS y puntajes bajos de MMSE. Puede concluirse que en pacientes con ECV y EPS, el aumento en RA incrementaría el riesgo de DC. Estos hallazgos enfatizan la necesidad de promover y mantener la salud bucal para evitar el DC en pacientes con ECV.

Cognitive impairment related to arterial stiffness in cardiovascular disease patients with severe periodontitis.

Severe periodontal disease (SPD) associated with systemic peripheral inflammation, cognitive impairment (CI) and arterial stiffness (AS) has been recognized. The aim of this study was to investigate whether CI and arterial stiffness (AS) occur in cardiovascular disease (CVD) patients with SPD. A crosssectional case-control study included hospitalized patients with CVD. Demographic characteristics, CVD and atherogenic risk factors were recorded. SPD was diagnosed by clinical and radiographic dental examinations. Dental clinical attachment level (CAL) and CAL % were recorded. A Mini-Mental State Examination test (MMSE) assessed cognition, a MMSE score of < 27 was set as the cut-off point of CI; a score ≥ 27 was considered as no CI. Patients were categorized into: MMSE<27 (cases) and MMSE≥27 (controls). AS was evaluated by pulse wave velocity (PWV). Serum VCAM-1 levels were determined in a random sample. Results: This study comprised 91 patients (cases, n=26; 29.6%; controls, n=65, 71.4%); aged 73±8 vs. 73±7 years, respectively (p=0.73), of whom 53.8% and 36.9% respectively, were women; SPD was found to be a risk factor for CI; the presence of SPD increased the risk for MMSE <27 by an average 5.39 times (model 1). PWV was associated with MMSE < 27 in the three models. The risk of having MMSE < 27 increased an average of 2.404-fold for each 1-unit increase in PWV. SPD and AS had significant and independent associations on the risk for development CI. MMSE negatively correlated with CAL% (r=0.69) and PWV (r=0.70). PWV positively correlated with CAL% (r=0.67). Serum VCAM-1 levels were higher in SPD with lower MMSE scores. In conclusion, SPD increases the risk of development of cognitive decline in CVD patients. PWV was directly associated with the risk of cognitive decline. These findings denote a significant opportunity to improve periodontal health in order to avert CI in CVD patients.

La enfermedad periodontal severa (EPS) podría estar asociada a la rigidez arterial (RA) y al deterioro cognitivo (DC). Se realizó un estudio transversal de casos y controles y se investigó la presencia de RA y DC en pacientes con enfermedad cardiovascular (ECV) y EPS. En pacientes hospitalizados con ECV se registraron las características demográficas y factores de riesgo aterogénicos. El DC se diagnosticó a través del Mini-Mental State Examination (MMSE). Punto de corte: MMSE<27 (casos); puntaje ≥27 ausencia de DC (controles). La EPS fue diagnosticada clínica y radiográficamente. Se registraron el nivel inserción clínica (NIC) y NIC %. La RA fue evaluada a través de la velocidad de onda de pulso (VOP). VCAM-1 sérico se determinó en una muestra aleatoria. Se incluyeron 91 pacientes (casos,n=26; 29.6%; controles,n=65, 71.4%); edad promedio: 73±8 vs. 73±7 años, respectivamente (p=0.73); % de mujeres: 53.8 vs. 36.9, respectivamente y EPS (n=54) y ausencia de EP (noEP) en 37. MMSE< 27 en 26 pacientes; 23 de ellos, con EPS. La presencia de EPS aumentó el riesgo de MMSE< 27 en 5.39 veces (modelo 1). La VOP se asoció a MMSE< 27 (Modelo 1, 2 y 3). El riesgo de MMSE< 27 incrementó en promedio en 2.40 veces por cada aumento de unidad de VOP. EPS y RA mostraron asociaciones significativas e independientes sobre el riesgo de DC. MMSE se correlacionó negativamente con NIC % (r=0.69) y POV (r=0.70); y POV, positivamente con NIC % (r=0.67). Los niveles séricos de VCAM-1 fueron más elevados en presencia de EPS y puntajes bajos de MMSE. Puede concluirse que en pacientes con ECV y EPS, el aumento en RA incrementaría el riesgo de DC. Estos hallazgos enfatizan la necesidad de promover y mantener la salud bucal para evitar el DC en pacientes con ECV.

Effect of angiotensin-converting enzyme inhibitors on vascular endothelial function in hypertensive patients after intensive periodontal treatment.

There is a relation between vascular endothelial function, atherosclerotic disease, and inflammation. Deterioration of endothelial function has been observed twenty-four hours after intensive periodontal treatment. This effect may be counteracted by the action of angiotensin-converting enzyme inhibitors, which improve endothelial function. The aim of the present study was to evaluate vascular endothelial function after intensive periodontal treatment, in hypertensive patients treated with angiotensinconverting enzyme inhibitors. A prospective, longitudinal, comparative study involving repeated measurements was conducted. Fifty-two consecutive patients with severe periodontal disease were divided into two groups, one comprising hypertensive patients treated with converting enzyme inhibitors and the other comprising patients with no clinical signs of pathology and not receiving angiotensin-converting enzyme inhibitors. Endothelial function was assessed by measuring postischemic dilation of the humeral artery (baseline echocardiography Doppler), and intensive periodontal treatment was performed 24h later. Endothelial function was re-assessed 24h and 15 days after periodontal treatment. STATISTICAL ANALYSIS: Results were analyzed using the SPSS 20 statistical software package. Student's t test and MANOVA were calculated and linear regression analysis with 95% confidence intervals and α<0.05 was performed. Arterial dilation at 24 hours was lower compared to baseline in both groups; values corresponding to the groups receiving angiotensin-converting enzyme inhibitors were 11.89 ± 4.87 vs. 7.30 ± 2.90% (p<0.01) and those corresponding to the group not receiving ACE inhibitors were 12.72 ± 4.62 vs. 3.56 ± 2.39 (p<0.001). The differences between groups were statistically significant (p<0.001). CONCLUSION: The increase in endothelial dysfunction after intensive periodontal treatment was significantly lower in hypertensive patients treated with angiotensin-converting enzyme inhibitors. Endothelial function improved 15 days after periodontal treatment, reaching baseline values. These results support the protective effect of angiotensin converting enzyme inhibitors on the endothelial function after intensive periodontal treatment.

Existe relación entre la disfunción del endotelio vascular, la enfermedad aterosclerótica y la inflamación. A las 24 h del tratamiento intensivo de la enfermedad periodontal se produce un deterioro de la función endotelial. Este efecto podría ser balanceado por la acción de los inhibidores de la enzima convertidora de la angiotensina que mejoran la función endotelial. El objetivo del presente estudio fue evaluar la función endotelial vascular después del tratamiento periodontal intensivo, en pacientes hipertensos tratados con inhibidores de la enzima convertidora de la angiotensina. Se realizó un estudio prospectivo, longitudinal, comparativo, con mediciones repetidas. Se incorporaron 52 pacientes consecutivos, con enfermedad periodontal severa divididos en dos grupos, uno con hipertensión arterial tratados con inhibidores de la enzima convertidora y el otro sin inhibidores ni patología clínicamente evidente. Se determinó la función endotelial cuantificando la dilatación de la arterial humeral post isquemia ecocardiografía Doppler basal. A las 24 h se efectuó el tratamiento periodontal intensivo; a 24 h y 15 días posteriores se reevaluó la función endotelial. Análisis estadístico: se empleó el paquete estadístico SPSS 20. Se realizaron: t-test de Student, MANOVA y análisis de regresión lineal con intervalos de confianza del 95% y α <0.05. Resultados: a las 24 h post tratamiento periodontal se observó una menor dilatación arterial en ambos grupos en relación a la dilatación arterial basal, siendo para el grupo con inhibidores 11.89 ±4.87 vs. 7.30 ± 2.90%, p<0.01 y para el grupo sin inhibidores 12.72 ± 4.62 vs 3.56 ± 2.39, p<0.001, con diferencias significativas entre ambos p< 0.001. En conclusión el aumento de la disfunción endotelial post tratamiento intensivo periodontal fue significativamente menor en hipertensos que recibieron inhibidores de la enzima convertidora de la angiotensina. La función endotelial mejoró a los 15 días de efectuado el tratamiento, alcanzando los valores inciales. Estos resultados permitirían relacionar a los inhibidores de la enzima convertidora con un efecto protector del endotelio posterior al tratamiento intensivo de la enfermedad periodontal.

Effect of angiotensin-converting enzyme inhibitors on vascular endothelial function in hypertensive patients after intensive periodontal treatment / Efecto de los inhibidores de la enzima convertidora sobre la función del endotelio vascular en pacientes hipertensos que recibieron tratamiento periodontal intensivo

There is a relation between vascular endothelial function,atherosclerotic disease, and inflammation. Deterioration ofendothelial function has been observed twenty-four hours afterintensive periodontal treatment. This effect may be counteractedby the action of angiotensin-converting enzyme inhibitors, whichimprove endothelial function. The aim of the present study was toevaluate vascular endothelial function after intensive periodontaltreatment, in hypertensive patients treated with angiotensin-converting enzyme inhibitors. A prospective, longitudinal, comparative study involving repeatedmeasurements was conducted. Fifty-two consecutive patients withsevere periodontal disease were divided into two groups, onecomprising hypertensive patients treated with converting enzymeinhibitors and the other comprising patients with no clinical signsof pathology and not receiving angiotensin-converting enzymeinhibitors. Endothelial function was assessed by measuring post-ischemic dilation of the humeral artery (baseline echocardiographyDoppler), and intensive periodontal treatment was performed 24hlater. Endothelial function was re-assessed 24h and 15 days after periodontal treatment. Statistical analysis: Results were analyzedusing the SPSS 20 statistical software package. Student’s t test andMANOVA were calculated and linear regression analysis with 95%confidence intervals and α<0.05 was performed. Arterial dilationat 24 hours was lower compared to baseline in both groups; valuescorresponding to the groups receiving angiotensin-convertingenzyme inhibitors were 11.89 ± 4.87 vs. 7.30 ± 2.90% (p<0.01) andthose corresponding to the group not receiving ACE inhibitors were12.72 ± 4.62 vs. 3.56 ± 2.39 (p<0.001). The differences betweengroups were statistically significant (p<0.001)...

Existe relación entre la disfunción del endotelio vascular, la enfermedad ateroesclerótica y la inflamación. A las 24 horas del tratamiento intensivo de la enfermedad periodontal, se produce un deterioro de la función endotelial. Este efecto podría ser balanceado por la acción de los inhibidores de la enzima convertidora de la angiotensina que mejoran la función endotelial. El objetivo del presente estudio fue evaluar la función endotelial vascular después del tratamiento periodontal intensivo, en pacientes hipertensos tratados con inhibidores de la enzima convertidora de la angiotensina. Se realizó un estudio prospectivo, longitudinal, comparativo, con mediciones repetidas. Se incorporaron 52 pacientes con enfermedad periodontal severa divididos en dos grupos, uno con hipertensión arterial, tratados con inhibidores de la enzima convertidora y otro sin inhibidores ni patología clínicamente evidente. Se determinó la función endotelial cuantificando la dilatación de la arterial humeral post isquemia ecocardiografía Doppler basal. A las 24 hs se efectuó el tratamiento periodontal intensivo; a las 24 h y 15 días posteriores se reevaluó la función endotelial. Análisis estadístico: se empleó el paquete estadístico SPSS 20. Se realizaron: t-test de Student, MANOVA y análisis de regresión lineal con intervalos de confianza del 95 por ciento y a <0.05. Resultados: a las 24 h post tratamiento periodontal, se observó una menor dilatación arterial en ambos grupos, en relación a la dilatación arterial basal, siendo para el grupo con inhibidores 11.89 +- 4.87 vs. 7.30 +- 2.90 por ciento, p<0.01 y para el grupo sin inhibidores 12.72 +- 4.62 vs. 3.56 +- 2.39, p<0.001, con diferencias significativas entre ambos p<0.001...

Papel de la tiorredoxina-1 en el atontamiento cardíaco en ratones transgénicos / Role of Thioredoxin-1 on Myocardial Stunning in Transgenic Mice

Introducción: La disfunción ventricular posisquémica (miocardio atontado) involucra un aumento del estrés oxidativo. En este sentido, la célula cuenta con mecanismos de defensa, como la tiorredoxina-1, un antioxidante que protege al miocardio de la lesión por isquemia/reperfusión, reduciendo el tamaño del infarto. Objetivo: Evaluar el comportamiento de la función ventricular sistólica y diastólica, particularmente estudiando la rigidez miocárdica y la relajación isovolúmica en el miocardio atontado en diferentes ratones transgénicos. Material y métodos: Se utilizaron corazones de ratones que sobreexpresan tiorredoxina-1 y de ratones transgénicos que sobreexpresan tiorredoxina-1 mutada en su sitio activo (dominante negativo), comparados con los de ratones no transgénicos, los cuales fueron sometidos a 15 minutos de isquemia global y 30 minutos de reperfusión utilizando la técnica de Langendorff. Se evaluó la función ventricular sistólica y diastólica y se calculó el t63 y el t93 como índice de relajación isovolúmica. Resultados: Las mediciones a los 30 minutos de reperfusión mostraron una mejoría significativa del estado contráctil en los ratones tiorredoxina-1 (57,4 ± 4,9 mm Hg; p ≤ 0,05 vs. no transgénicos) y también en la rigidez (11,8 ± 2,9 mm Hg; p ≤ 0,05 vs. no transgénicos). Por otra parte, en los ratones dominantes negativos se observó un aumento de la rigidez (37,7 ± 5,5 mm Hg; p ≤ 0,05 vs. no transgénicos) y un enlentecimiento de la relajación a los 30 minutos de la reperfusión (78,2 ± 9,8 mseg; p ≤ 0,05 vs. no transgénicos). Conclusión: Este trabajo evidencia el rol protector de la tiorredoxina-1 en el miocardio atontado y su importancia fisiopatológica en ratones que sobreexpresan este antioxidante.

Background: Postischemic ventricular dysfunction (myocardial stunning) involves increased oxidative stress. In this sense, the cell has defense mechanisms, as thioredoxin-1, an antioxidant that protects the myocardium from ischemia/reperfusion injury, reducing infarct size. Objective: The aim of this study was to evaluate systolic and diastolic ventricular function, specifically analyzing myocardial stiffness and isovolumic relaxation, during myocardial stunning in different transgenic mice. Methods: Hearts from mice overexpressing thioredoxin-1 and transgenic mice overexpressing thioredoxin-1 with gene mutation in its active site (dominant negative) were compared with hearts from non-transgenic mice after 15-minute global ischemia and 30-minute reperfusion using the Langendorff technique. Systolic and diastolic ventricular function was evaluated and t63 and t93 were calculated as ventricular relaxation index. Results: At 30-minute reperfusion, thioredoxin-1 mice showed a significantly improved contractile state (57.4±4.9 mmHg; p≤0.05 vs. non-transgenic mice) and stiffness (11.8±2.9 mmHg; p≤0.05 vs. non-transgenic mice). Conversely, at the same reperfusion time, dominant negative mice exhibited increased stiffness (37.7±5.5 mmHg; p≤0.05 vs. non-transgenic mice) and slower relaxation (78.2±9.8 ms; p≤0.05 vs. non-transgenic mice). Conclusion: This study reveals the protective role of thioredoxin-1 on myocardial stunning and its pathophysiological importance in mice overexpressing this antioxidant.

Effect of oral hygiene and 0.12% chlorhexidine gluconate oral rinse in preventing ventilator-associated pneumonia after cardiovascular surgery.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a nosocomial infection of multifactorial etiology and has a negative influence on cardiovascular surgery (CVS) outcomes. OBJECTIVES: Determine the effect of toothbrushing plus 0.12% chlorhexidine gluconate oral rinse in preventing VAP after CVS. METHODS: In a quasi-experimental study, patients undergoing heart surgery were enrolled in a protocol for controlling dental biofilm by proper oral hygiene (toothbrushing) and oral rinses with 0.12% chlorhexidine gluconate (Group 1), and they were compared with a historical control group (Group 2), which included patients who underwent cardiac surgery between 2009 and 2010 and who received regular oral hygiene care. Seventy-two hours before surgery, a dentist provided instruction and supervised oral hygiene with toothbrushing and chlorhexidine oral rinses to patients in Group 1. RESULTS: Each group comprised 150 patients. A lower incidence of VAP (2.7% [95% CI 0.7-7.8] vs 8.7% [95% CI 4.9-14.7], P = .04) and a shorter hospital stay (9 ± 3 d [95% CI 8.5-9.5] vs 10 ± 4 d [95% CI 9.4-10.7], P = .01) were observed in Group 1. No significant differences in all-cause in-hospital death were observed between groups (5.3% vs 4.7%, P > .99). The risk for developing pneumonia after surgery was 3-fold higher in Group 2 (3.9, 95% CI 1.1-14.2). CONCLUSIONS: Oral hygiene and mouth rinses with chlorhexidine under supervision of a dentist proved effective in reducing the incidence of VAP.

Oxidative stress assessed in saliva from patients with acute myocardial infarction. A preliminary study.

UNLABELLED: There is evidence that acute myocardial infarction (AMI) is associated with increasing production of reactive oxygen species and tissue injury. The aim of this study was to assess the presence of oxidative stress indices in saliva 24 and 48h after AMI. MATERIALS AND METHODS: We designed a prospective study comparing salivary levels of biomarkers of oxidative stress in patients with AMI with elevation of the ST segment in electrocardiogram versus clinically healthy subjects. Oxidative stress indices including the rate of oxidation of 2'7' dichlorohydrofluorescein diacetate (DCFH-DA) and the activity of the antioxidant enzyme catalase (CAT) were evaluated in saliva from patients with AMI at 24 and 48 hours. At each sampling time, blood was drawn for serum markers of myocardial infarction. RESULTS: This study included ten patients with acute ST-segment elevation myocardial infarction and ten clinically healthy controls. Mean age was 67.8 +/- 11.1 vs. 48.7 +/- 4.1 years (p < 0.001) and gender was 60% male vs. 50% (p > 0.05) for AMI vs. controls, respectively. Our results demonstrated an increase in the rate of oxidation of DCFH-DA in the myocardial infarction group as compared with controls (p = 0.004), which remained unchanged at 48h. There was no difference in salivary catalase activity between controls and AML subjects at 24h or at 48h post-diagnosis (p = 0.157). The relationship between CAT48 and DCFH-DA48 was fairly significant (r = 0.39; p = 0.053). CONCLUSION: This preliminary study showed that biomarkers of oxidative stress are detectable in saliva of patients with acute myocardial infarction. CLINICAL RELEVANCE: Future studies using a larger population are needed to confirm these observations and to explore the possibility of using the saliva to monitor evolving diagnosis and prognosis in acute coronary syndrome.

Oxidative stress assessed in saliva from patients with acute myocardial infarction: a preliminary study

Existe evidencia que permite establecer una asociación entre la generación de especies reactivas del oxígeno y el daño tisular en el síndrome coronario agudo. El objetivo de este trabajo fue detectaren saliva de pacientes con infarto agudo de miocardio (IAM), la presencia de reactantes de estrés oxidativo a las 24 y 48 horas. Materiales y métodos: se efectuó un estudio prospectivo de comparación entre pacientes con IAM con supradesnivel del segmento STen el electrocardiograma y sujetos sin patología clínica evidente. Laproducción de especies reactivas de oxígeno fue evaluada mediantela tasa de oxidación de la 2’7’ diacetato de diclorohidrofluoreceina (DCFH-DA) y la actividad antioxidante de la enzima catalasa (CAT) en saliva de pacientes con IAM a las 24 y 48 h de producido el síndrome coronario agudo. Simultáneamente, se determinaron en suero los biomarcadores diagnósticos de IAM. Resultados: se incorporaron10 pacientes con IAM con supradesnivel del ST que fueron comparados con 10 sujetos del grupo control. La edad promedio fue 67.8 ± 11.1 vs 48.7 ± 4.1 años, respectivamente (p<0.001); el 60 por ciento vs 50 por ciento fueron hombres sin diferencias entre ambos grupos (p>0.05). La media de la velocidad de oxidación de la DCFH-DA fue mayor a las 24 h en los pacientes con IAM (p=0.004). Estas diferencias semantuvieron a las 48 h del infarto sin cambios significativos. No se encontraron diferencias en las medias de actividad de la enzima catalasa entre IAM y control (p>0.05). Se encontró una relación entre CAT48 y DCFH-DA48 (r=0.39; p=0.053). Conclusiones: Enesta población se han detectado reactantes de estrés oxidativo ensaliva de pacientes con IAM. Relevancia clínica: nuevos estudios con mayor número de casos serán necesarios para confirmar estas observaciones y evaluar la utilidad de la saliva en el diagnóstico,evolución y pronóstico del síndrome coronario agudo.

There is evidence that acute myocardial infarction (AMI) is asso-ciated with increasing production of reactive oxygen species andtissue injury. The aim of this study was to assess the presence ofoxidative stress indices in saliva 24 and 48h after AMI. Materialsand methods: We designed a prospective study comparing sali-vary levels of biomarkers of oxidative stress in patients with AMIwith elevation of the ST segment in electrocardiogram versus clin-ically healthy subjects. Oxidative stress indices including the rateof oxidation of 2’7’ dichlorohydrofluorescein diacetate (DCFH-DA) and the activity of the antioxidant enzyme catalase (CAT)were evaluated in saliva from patients with AMI at 24 and 48hours. At each sampling time, blood was drawn for serum mark-ers of myocardial infarction. Results: This study included tenpatients with acute ST-segment elevation myocardial infarctionand ten clinically healthy controls. Mean age was 67.8 ± 11.1 vs.48.7 ± 4.1 years (p<0.001) and gender was 60% male vs. 50%(p>0.05) for AMI vs. controls, respectively. Our results demon-strated an increase in the rate of oxidation of DCFH-DA in themyocardial infarction group as compared with controls (p=0.004),which remained unchanged at 48h. There was no difference insalivary catalase activity between controls and AMI subjects at24h or at 48h post-diagnosis (p=0.157). The relationship betweenCAT48and DCFH-DA48was fairly significant (r=0.39; p=0.053).Conclusion: This preliminary study showed that biomarkers ofoxidative stress are detectable in saliva of patients with acutemyocardial infarction. Clinical Relevance: Future studies using alarger population are needed to confirm these observations and toexplore the possibility of using the saliva to monitor evolving diag-nosis and prognosis in acute coronary syndrome.

Oxidative stress assessed in saliva from patients with acute myocardial infarction: a preliminary study

Existe evidencia que permite establecer una asociación entre la generación de especies reactivas del oxígeno y el daño tisular en el síndrome coronario agudo. El objetivo de este trabajo fue detectaren saliva de pacientes con infarto agudo de miocardio (IAM), la presencia de reactantes de estrés oxidativo a las 24 y 48 horas. Materiales y métodos: se efectuó un estudio prospectivo de comparación entre pacientes con IAM con supradesnivel del segmento STen el electrocardiograma y sujetos sin patología clínica evidente. Laproducción de especies reactivas de oxígeno fue evaluada mediantela tasa de oxidación de la 2Æ7Æ diacetato de diclorohidrofluoreceina (DCFH-DA) y la actividad antioxidante de la enzima catalasa (CAT) en saliva de pacientes con IAM a las 24 y 48 h de producido el síndrome coronario agudo. Simultáneamente, se determinaron en suero los biomarcadores diagnósticos de IAM. Resultados: se incorporaron10 pacientes con IAM con supradesnivel del ST que fueron comparados con 10 sujetos del grupo control. La edad promedio fue 67.8 ± 11.1 vs 48.7 ± 4.1 años, respectivamente (p<0.001); el 60 por ciento vs 50 por ciento fueron hombres sin diferencias entre ambos grupos (p>0.05). La media de la velocidad de oxidación de la DCFH-DA fue mayor a las 24 h en los pacientes con IAM (p=0.004). Estas diferencias semantuvieron a las 48 h del infarto sin cambios significativos. No se encontraron diferencias en las medias de actividad de la enzima catalasa entre IAM y control (p>0.05). Se encontró una relación entre CAT48 y DCFH-DA48 (r=0.39; p=0.053). Conclusiones: Enesta población se han detectado reactantes de estrés oxidativo ensaliva de pacientes con IAM. Relevancia clínica: nuevos estudios con mayor número de casos serán necesarios para confirmar estas observaciones y evaluar la utilidad de la saliva en el diagnóstico,evolución y pronóstico del síndrome coronario agudo.(AU)

There is evidence that acute myocardial infarction (AMI) is asso-ciated with increasing production of reactive oxygen species andtissue injury. The aim of this study was to assess the presence ofoxidative stress indices in saliva 24 and 48h after AMI. Materialsand methods: We designed a prospective study comparing sali-vary levels of biomarkers of oxidative stress in patients with AMIwith elevation of the ST segment in electrocardiogram versus clin-ically healthy subjects. Oxidative stress indices including the rateof oxidation of 2Æ7Æ dichlorohydrofluorescein diacetate (DCFH-DA) and the activity of the antioxidant enzyme catalase (CAT)were evaluated in saliva from patients with AMI at 24 and 48hours. At each sampling time, blood was drawn for serum mark-ers of myocardial infarction. Results: This study included tenpatients with acute ST-segment elevation myocardial infarctionand ten clinically healthy controls. Mean age was 67.8 ± 11.1 vs.48.7 ± 4.1 years (p<0.001) and gender was 60% male vs. 50%(p>0.05) for AMI vs. controls, respectively. Our results demon-strated an increase in the rate of oxidation of DCFH-DA in themyocardial infarction group as compared with controls (p=0.004),which remained unchanged at 48h. There was no difference insalivary catalase activity between controls and AMI subjects at24h or at 48h post-diagnosis (p=0.157). The relationship betweenCAT48and DCFH-DA48was fairly significant (r=0.39; p=0.053).Conclusion: This preliminary study showed that biomarkers ofoxidative stress are detectable in saliva of patients with acutemyocardial infarction. Clinical Relevance: Future studies using alarger population are needed to confirm these observations and toexplore the possibility of using the saliva to monitor evolving diag-nosis and prognosis in acute coronary syndrome.(AU)

Oxidative stress assessed in saliva from patients with acute myocardial infarction. A preliminary study. / Oxidative stress assessed in saliva from patients with acute myocardial infarction. A preliminary study.

UNLABELLED: There is evidence that acute myocardial infarction (AMI) is associated with increasing production of reactive oxygen species and tissue injury. The aim of this study was to assess the presence of oxidative stress indices in saliva 24 and 48h after AMI. MATERIALS AND METHODS: We designed a prospective study comparing salivary levels of biomarkers of oxidative stress in patients with AMI with elevation of the ST segment in electrocardiogram versus clinically healthy subjects. Oxidative stress indices including the rate of oxidation of 27 dichlorohydrofluorescein diacetate (DCFH-DA) and the activity of the antioxidant enzyme catalase (CAT) were evaluated in saliva from patients with AMI at 24 and 48 hours. At each sampling time, blood was drawn for serum markers of myocardial infarction. RESULTS: This study included ten patients with acute ST-segment elevation myocardial infarction and ten clinically healthy controls. Mean age was 67.8 +/- 11.1 vs. 48.7 +/- 4.1 years (p < 0.001) and gender was 60

male vs. 50

(p > 0.05) for AMI vs. controls, respectively. Our results demonstrated an increase in the rate of oxidation of DCFH-DA in the myocardial infarction group as compared with controls (p = 0.004), which remained unchanged at 48h. There was no difference in salivary catalase activity between controls and AML subjects at 24h or at 48h post-diagnosis (p = 0.157). The relationship between CAT48 and DCFH-DA48 was fairly significant (r = 0.39; p = 0.053). CONCLUSION: This preliminary study showed that biomarkers of oxidative stress are detectable in saliva of patients with acute myocardial infarction. CLINICAL RELEVANCE: Future studies using a larger population are needed to confirm these observations and to explore the possibility of using the saliva to monitor evolving diagnosis and prognosis in acute coronary syndrome.

Tratamiento periodontal intensivo en pacientes con enfermedad coronaria / Intensive periodontal treatment in patients with cardiovascular diseases

El objetivo del trabajo fue determinar si el tratamiento periodontal intensivo(TPI), es seguro de realizar en pacientes de alto riesgo (AR) cardiovascular. Para ello se estudiaron 20 pacientes con enfermedad Periodontal severa que participaron del estudio FEEP1 (Función Endotelial y Enfermedad Periodontal), que presentaran AR. El TPI consistió en el raspaje y alisado de todas las piezas afectadas por enfermedad Periodontal, en una sola sesión.Todos los pacientes fueron controlados cardiológicamente24hs. previas y posteriores al TPI, asícomo a los 15 días. Se monitoreó la frecuencia cardíaca, tensión arterial y oximetría de pulso. Resultados:Durante el tratamiento odontológico y/o con posterioridad al mismo, ninguno de los pacientes desarrolló sintomatologíacompatible con isquemia miocárdica nicomplicaciones cardiovasculares. Conclusiones: El tratamiento Periodontal intensivo, resultó ser seguro en elgrupo de pacientes cardiovascularmente estables con cardiopatía isquémica de alto riesgo estudiados.

Tratamiento periodontal intensivo en pacientes con enfermedad coronaria / Intensive periodontal treatment in patients with cardiovascular diseases

El objetivo del trabajo fue determinar si el tratamiento periodontal intensivo(TPI), es seguro de realizar en pacientes de alto riesgo (AR) cardiovascular. Para ello se estudiaron 20 pacientes con enfermedad Periodontal severa que participaron del estudio FEEP1 (Función Endotelial y Enfermedad Periodontal), que presentaran AR. El TPI consistió en el raspaje y alisado de todas las piezas afectadas por enfermedad Periodontal, en una sola sesión.Todos los pacientes fueron controlados cardiológicamente24hs. previas y posteriores al TPI, asícomo a los 15 días. Se monitoreó la frecuencia cardíaca, tensión arterial y oximetría de pulso. Resultados:Durante el tratamiento odontológico y/o con posterioridad al mismo, ninguno de los pacientes desarrolló sintomatologíacompatible con isquemia miocárdica nicomplicaciones cardiovasculares. Conclusiones: El tratamiento Periodontal intensivo, resultó ser seguro en elgrupo de pacientes cardiovascularmente estables con cardiopatía isquémica de alto riesgo estudiados. (AU)

Comparative study of changes in arterial pressure and heart rate during dental treatment under local anesthesia in hypertensive patients versus normotensive patients.

The aim of this study was to determine changes in arterial pressure (AP) and heart rate (HR) during dental treatment under local infiltration anesthesia (LIA) in patients with controlled arterial hypertension (AHT) versus normotensive patients. A longitudinal comparative study involving repeated measurements in well-controlled hypertensive (cases) and normotensive patients (controls) was conducted. All patients received standardized preventive periodontal treatment under LIA (1.8 ml of 4% articaine with 1:100000 L-Adrenaline). AP and HR were determined at 5 different phases of treatment. The study comprised 82 patients, 46.3% of whom were hypertensive, 61% were female. Systolic (SAP) and diastolic (DAP) arterial pressure and HR increased as the procedure advanced and then returned to initial values in both groups. Average HR values were lower in normotensive than in hypertensive patients (p < 0.001). Significant differences in AP and HR were observed among initial, mid-procedure, and final values (p < 0.001). Both groups exhibited highest SAP values post-LIA administration (p < 0.01). Average HR was higher in normotensive than in hypertensive patients. The hypertensive patients tended to develop AHT (> 140/90 mmHg) more frequently throughout the procedure (p = 0.002), SHOWING a 4.93-fold higher risk. Logistic regression analysis showed that sex (p < 0.032) and AH (p < 0.007) were associated with a tendency to develop AHT during treatment. Controlled hypertensive patients with normal AP values at the onset of dental treatment were found to be at a 5-fold higher risk of developing AHT during the course of dental treatment under local infiltration anesthesia. The observed increases in AP, however, did not reach clinically significant levels. The HR values tended to increase with the progress of dental treatment in all patients. HR was lower in hypertensive patients probably due a drug effect.