Traqueostomías en pacientes con SARS COV-2 Protocolo de seguridad del equipo de cabeza y cuello / TRACHEOSTOMY IN PATIENTS WITH SARS CoV-2 HEAD AND NECK EQUIPMENT SAFETY PROTOCOL

Introducción: El virus SARS-CoV-2, se presentó en la ciudad de Wuhan, una provincia de Hubei en China, a finales del mes de diciembre de 2019, como un brote de neumonía viral consecuencia de un nuevo tipo de coronavirus B, el cual fue denominado COVID-19; posteriormente, de manera oficial, se declarará al virus como SARS-Cov-2. Los cirujanos de cabeza y cuello realizan traqueostomías en pacientes con COVID-19, lo que supone mayor exposición de aerosolización para estos especialistas. El presente trabajo tiene como finalidad describir la técnica quirúrgica de la traqueostomía abierta con la adecuada protección del equipo de cirugía de cabeza y cuello en los pacientes con SAR-CoV-2-. Métodos: Este estudio se realizó en el Centro Médico Docente la Trinidad, a cargo del servicio de cabeza y cuello. El equipo multidisciplinario estuvo conformado por cirujanos de cabeza y cuello, intensivistas y enfermeros especialistas del área. La traqueostomía fue abierta y fue realizada en los pacientes ingresados en la unidad de cuidados intensivos con resultado positivo de la infección por SARS-CoV-2, en el periodo entre agosto de 2020 a agosto de 2021, previa discusión con el equipo multidisciplinario y con el consentimiento de los familiares del paciente, idealmente, entre el día 15 y 21. Resultados: Se realizaron 14 traqueotomías abiertas, la primera traqueostomía se llevó a cabo el 01/08/2020 y la ultima el 28/08/2021. Todas fueron realizadas en la unidad de terapia intensiva. El personal médico fue el mínimo posible y consto de: Cirujano de cabeza y cuello, primer y segundo ayudante, instrumentista, intensivista, residente de terapia intensiva y enfermera de terapia intensiva. En todos los casos se llevó a cabo la adecuada higiene de manos y colocación del equipo de protección personal. Conclusiones: Mantener a los pacientes relajados durante el procedimiento, desinflar el manguito del tubo endotraqueal y cerrar el circuito previo a la incisión y rápidamente luego de la incisión en tráquea, insertar el traqueostomo y conectar el sistema de circuito cerrado, parece ser una técnica que preserva la seguridad del equipo quirúrgico

Introduction: The SARS-CoV-2 virus appeared in the city of Wuhan, a province of Hubei in China, at the end of December 2019, as an outbreak of viral pneumonia because of a new type of coronavirus B, the was called COVID-19; later, officially, the virus will be declared as SARS-Cov-2. Head and neck surgeons perform tracheostomies in patients with CIVD-19, which results in increased aerolization exposure. The present work aims to describe the surgical technique of open tracheostomy with adequate protection of the head and neck surgery team in patients with SAR-CoV-2. Methods: This study was carried out at the La Trinidad Teaching Medical Center, in charge of the head and neck service. The multidisciplinary team was made up of head and neck surgeons, intensivists, and specialist nurses in the area. The technique was open tracheostomy in patients admitted to the intensive care unit with a positive result for SARS-CoV-2 infection, in the period between August 2020 to August 2021, after discussion with the multidisciplinary team and with the consent of the patient's relatives, ideally between the 15th and 21st. Results: 14 open tracheostomies were performed, the first tracheostomy was performed on 01 / 08/2020 and the last one on 08/28/2021. All tracheostomies were performed in the intensive care unit. The medical staff was the minimum possible and consisted of: Head and neck surgeon, first and second assistant, scrub nurse, intensivist, intensive care resident and intensive care nurse. In all cases, proper hand hygiene and placement of personal protective equipment was carried out. Conclusions: Keeping patients relaxed during the procedure, deflating the endotracheal tube cuff, and closing the circuit prior to the incision and quickly after the incision in the trachea and inserting the tracheostoma, connecting the closed-circuit system, seems to be a technique that preserves the safety of the surgical team

Effects of Naringin on Cardiomyocytes From a Rodent Model of Type 2 Diabetes.

Diabetic cardiomyopathy (DCM) is a primary disease in diabetic patients characterized by diastolic dysfunction leading to heart failure and death. Unfortunately, even tight glycemic control has not been effective in its prevention. We have found aberrant diastolic Ca2+ concentrations ([Ca2+]d), decreased glucose transport, elevated production of reactive oxygen species (ROS), and increased calpain activity in cardiomyocytes from a murine model (db/db) of type 2 diabetes (T2D). Cardiomyocytes from these mice demonstrate significant cell injury, increased levels of tumor necrosis factor-alpha and interleukin-6 and expression of the transcription nuclear factor-κB (NF-κB). Furthermore, decreased cell viability, and reduced expression of Kir6.2, SUR1, and SUR2 subunits of the ATP-sensitive potassium (KATP) channels. Treatment of T2D mice with the citrus fruit flavonoid naringin for 4 weeks protected cardiomyocytes by reducing diastolic Ca2+ overload, improving glucose transport, lowering reactive oxygen species production, and suppressed myocardial inflammation. In addition, naringin reduced calpain activity, decreased cardiac injury, increased cell viability, and restored the protein expression of Kir6.2, SUR1, and SUR2 subunits of the KATP channels. Administration of the KATP channel inhibitor glibenclamide caused a further increase in [Ca2+]d in T2D cardiomyocytes and abolished the naringin effect on [Ca2+]d. Nicorandil, a KATP channel opener, and nitric oxide donor drug mimic the naringin effect on [Ca2+]d in T2D cardiomyocyte; however, it aggravated the hyperglycemia in T2D mice. These data add new insights into the mechanisms underlying the beneficial effects of naringin in T2D cardiomyopathy, thus suggesting a novel approach to treating this cardiovascular complication.

Pro-arrhythmogenic effects of Trypanosoma cruzi conditioned medium proteins in a model of bovine chromaffin cells.

Asymptomatic sudden death is the principal cause of mortality in Chagas disease. There is little information about molecular mechanisms involved in the pathophysiology of malignant arrhythmias in Chagasic patients. Previous studies have involved Trypanosoma cruzi secretion proteins in the genesis of arrhythmias ex vivo, but the molecular mechanisms involved are still unresolved. Thus, the aim was to determine the effect of these secreted proteins on the cellular excitability throughout to test its effects on catecholamine secretion, sodium-, calcium-, and potassium-conductance and action potential (AP) firing. Conditioned medium was obtained from the co-culture of T. cruzi and Vero cells (African green monkey kidney cells) and ultra-filtered for concentrating immunogenic high molecular weight parasite proteins. Chromaffin cells were assessed with the parasite and Vero cells control medium. Parasite-secreted proteins induce catecholamine secretion in a dose-dependent manner. Additionally, T. cruzi conditioned medium induced depression of both calcium conductance and calcium and voltage-dependent potassium current. Interestingly, this fact was related to the abolishment of the hyperpolarization phase of the AP produced by the parasite medium. Taken together, these results suggest that T. cruzi proteins may be involved in the genesis of pro-arrhythmic conditions that could influence the appearance of malignant arrhythmias in Chagasic patients.

Ex vivo trypanocidal activity of 1-(2-hydroxybenzylidene)thiosemicarbazide against Trypanosoma equiperdum.

Trypanosoma equiperdum is the causative agent of dourine, a venereal disease in horses and donkeys. This parasite has a widely distribution, is found in Africa, Asia, Southern and Eastern Europe, Russia, Mexico and Venezuela. The T. equiperdum is morphologically indistinguishable to other Trypanozoon species, however differs from other mammalian trypanosomes due to the fact that it is primarily a tissue parasite, generating cutaneous plaques, swelling of genitalia and neurological signs. The aim of this study was to evaluate the trypanocidal effectiveness of a set of derivatives of thiosemicarbazones on a T. equiperdum ex vivo culture. All compounds appeared to have trypanocidal activity, however one of them shown better solubility and a dose-dependent effect. The median inhibitory concentration (IC50) was 1.2µM. The selected compound exhibits a greater inhibitory activity than diminazene aceturate, a common drug for animal trypanosomosis treatment.

Salivary glucose as a metabolic control marker in patients with type 2 diabetes.

A study was made of the correlation between the serum and salivary glucose levels in healthy subjects and in patients with type 2 diabetes, in order to establish the validity of salivary glucose determination in monitoring glycemia. Ninety-seven subjects were included in the study: 47 diabetic patients and 46 controls, aged between 40- and 80-years-of-age. Venous blood and saliva samples were collected in both groups under fasting conditions and after administering a test meal (15% proteins, 55% carbohydrates and 30% lipids). The glucose levels were measured using the glucose oxidase technique. The salivary glucose levels were seen to be greater in the diabetic group vs the controls both under fasting conditions (baseline) and after the meal (postprandial) (p=0.023 and p=0.008, respectively). A significant positive correlation was found between the serum and salivary glucose levels at baseline and under resting conditions, particularly in the diabetic group (r=0.389, p=0.002). The coefficient of determination of the simple linear regression model was R2=0.042, showing salivary glucose to be related to the blood glucose levels. In conclusion, salivary glucose concentration is correlated to serum glucose, particularly in type 2 diabetics.

Oxidative and endoplasmic reticulum stress is impaired in leukocytes from metabolically unhealthy vs healthy obese individuals.

BACKGROUND: Oxidative stress and inflammation are related to obesity, but the influence of metabolic disturbances on these parameters and their relationship with endoplasmic reticulum (ER) stress is unknown. Therefore, this study was performed to evaluate whether metabolic profile influences ER and oxidative stress in an obese population with/without comorbidities. SUBJECTS AND METHODS: A total of 113 obese patients were enrolled in the study; 29 were metabolically healthy (MHO), 53 were metabolically abnormal (MAO) and 31 had type 2 diabetes (MADO). We assessed metabolic parameters, proinflammatory cytokines (TNFα and IL-6), mitochondrial and total reactive oxygen species (ROS) production, glutathione levels, antioxidant enzymes activity, total antioxidant status, mitochondrial membrane potential and ER stress marker expression levels (glucose-regulated protein (GRP78), spliced X-box binding protein 1 (XBP1), P-subunit 1 alpha (P-eIF2α) and activating transcription factor 6 (ATF6). RESULTS: The MAO and MADO groups showed higher blood pressure, atherogenic dyslipidemia, insulin resistance and inflammatory profile than that of MHO subjects. Total and mitochondrial ROS production was enhanced in MAO and MADO patients, and mitochondrial membrane potential and catalase activity differed significantly between the MADO and MHO groups. In addition, decreases in glutathione levels and superoxide dismutase activity were observed in the MADO vs MAO and MHO groups. GRP78 and CHOP protein and gene expression were higher in the MAO and MADO groups with respect to MHO subjects, and sXBP1 gene expression was associated with the presence of diabetes. Furthermore, MAO patients exhibited higher levels of ATF6 than their MHO counterparts. Waist circumference was positively correlated with ATF6 and GRP78, and A1c was positively correlated with P-Eif2α. Interestingly, CHOP was positively correlated with TNFα and total ROS production and GRP78 was negatively correlated with glutathione levels. CONCLUSIONS: Our findings support the hypothesis that both inflammation and oxidative stress are involved in the induction of ER stress signaling pathways in the leukocytes of metabolically unhealthy obese vs healthy obese subjects.

Hiperaldosteronismo primario por hiperplasia suprarrenal unilateral con resolución quirúrgica / Primary hyperaldosteronism due to unilateral adrenal hyperplasia with surgical resolution

La hiperplasia suprarrenal unilateral es una causa rara de hiperaldosteronismo primario (sobre un 3%) que tiene tratamiento quirúrgico. Presentamos el caso de una mujer de 50 años con hipertensión arterial refractaria en tratamiento con 7 fármacos con hiperaldosteronismo primario por hiperplasia suprarrenal unilateral, que tras suprarrenalectomía izquierda presenta curación sin necesidad de ningún fármaco antihipertensivo tras 2 años desde la cirugía. La hiperplasia suprarrenal unilateral es una entidad diferente y no es una variante asimétrica de la hiperplasia bilateral. En el estudio de pacientes con hiperaldosteronismo primario y pruebas de imagen sin presencia de adenoma suprarrenal, es un diagnóstico que hay que considerar antes de catalogar a los pacientes con hiperplasia suprarrenal bilateral y de iniciar tratamiento médico, ya que la hiperplasia unilateral tendría resolución quirúrgica

Unilateral adrenal hyperplasia is a rare cause of primary hyperaldosteronism (around a 3%) that has surgical treatment. A case of a patient with hypertension resistant to conventional therapy in treatment with 7 drugs who presented with primary hyperaldosteronism due to unilateral adrenal hyperplasia is presented. A left adrenalectomy was performed, and the patient had a good clinical response, with no need of any drug after 2 years of surgery. Unilateral adrenal hyperplasia is a different entity and it is not an asymmetric variant of the bilateral adrenal hyperplasia. In the study of patients with primary hyperaldosteronism and imaging tests with absence of adenoma is a diagnosis that must be considered before cataloguing patients with bilateral adrenal hyperplasia and start a medical treatment, because unilateral adrenal hyperplasia would have a surgical resolution

[Primary hyperaldosteronism due to unilateral adrenal hyperplasia with surgical resolution]. / Hiperaldosteronismo primario por hiperplasia suprarrenal unilateral con resolución quirúrgica.

Unilateral adrenal hyperplasia is a rare cause of primary hyperaldosteronism (around a 3%) that has surgical treatment. A case of a patient with hypertension resistant to conventional therapy in treatment with 7 drugs who presented with primary hyperaldosteronism due to unilateral adrenal hyperplasia is presented. A left adrenalectomy was performed, and the patient had a good clinical response, with no need of any drug after 2 years of surgery. Unilateral adrenal hyperplasia is a different entity and it is not an asymmetric variant of the bilateral adrenal hyperplasia. In the study of patients with primary hyperaldosteronism and imaging tests with absence of adenoma is a diagnosis that must be considered before cataloguing patients with bilateral adrenal hyperplasia and start a medical treatment, because unilateral adrenal hyperplasia would have a surgical resolution.

Molecular characterization and classification of Trypanosoma spp. Venezuelan isolates based on microsatellite markers and kinetoplast maxicircle genes.

BACKGROUND: Livestock trypanosomoses, caused by three species of the Trypanozoon subgenus, Trypanosoma brucei brucei, T. evansi and T. equiperdum is widely distributed throughout the world and constitutes an important limitation for the production of animal protein. T. evansi and T. equiperdum are morphologically indistinguishable parasites that evolved from a common ancestor but acquired important biological differences, including host range, mode of transmission, distribution, clinical symptoms and pathogenicity. At a molecular level, T. evansi is characterized by the complete loss of the maxicircles of the kinetoplastic DNA, while T. equiperdum has retained maxicircle fragments similar to those present in T. brucei. T. evansi causes the disease known as Surra, Derrengadera or "mal de cadeiras", while T. equiperdum is the etiological agent of dourine or "mal du coit", characterized by venereal transmission and white patches in the genitalia. METHODS: Nine Venezuelan Trypanosoma spp. isolates, from horse, donkey or capybara were genotyped and classified using microsatellite analyses and maxicircle genes. The variables from the microsatellite data and the Procyclin PE repeats matrices were combined using the Hill-Smith method and compared to a group of T. evansi, T. equiperdum and T. brucei reference strains from South America, Asia and Africa using Coinertia analysis. Four maxicircle genes (cytb, cox1, a6 and nd8) were amplified by PCRfrom TeAp-N/D1 and TeGu-N/D1, the two Venezuelan isolates that grouped with the T. equiperdum STIB841/OVI strain. These maxicircle sequences were analyzed by nucleotide BLAST and aligned toorthologous genes from the Trypanozoon subgenus by MUSCLE tools. Phylogenetic trees were constructed using Maximum Parsimony (MP) and Maximum Likelihood (ML) with the MEGA5.1® software. RESULTS: We characterized microsatellite markers and Procyclin PE repeats of nine Venezuelan Trypanosoma spp. isolates with various degrees of virulence in a mouse model, and compared them to a panel of T. evansi and T. equiperdum reference strains. Coinertia analysis of the combined repeats and previously reported T. brucei brucei microsatellite genotypes revealed three distinct groups. Seven of the Venezuelan isolates grouped with globally distributed T. evansi strains, while TeAp-N/D1 and TeGu-N/D1 strains clustered in a separate group with the T. equiperdum STIB841/OVI strain isolated in South Africa. A third group included T. brucei brucei, two strains previously classified as T. evansi (GX and TC) and one as T. equiperdum (BoTat-1.1). Four maxicircle genes, Cytochrome b, Cythocrome Oxidase subunit 1, ATP synthase subunit 6 and NADH dehydrogenase subunit 8, were identified in the two Venezuelan strains clustering with the T. equiperdum STIB841/OVI strain. Phylogenetic analysis of the cox1 gene sequences further separated these two Venezuelan T. equiperdum strains: TeAp-N/D1 grouped with T. equiperdum strain STIB818 and T. brucei brucei, and TeGu-N/D1 with the T. equiperdum STIB841/OVI strain. CONCLUSION: Based on the Coinertia analysis and maxicircle gene sequence phylogeny, TeAp-N/D1 and TeGu-N/D1 constitute the first confirmed T. equiperdum strains described from Latin America.

Erratum to: Molecular characterization and classification of Trypanosoma spp. Venezuelan isolates based on microsatellite markers and kinetoplast maxicircle genes.

Unfortunately, the original version of this article [1] contained an error. Figure 1 in the original article, corresponded to the first coinertia analysis that was carried out with no data on the procyclin PE repeats for the T. brucei brucei strains. After including these data, the coinertia analysis was modified both in the directionality of the arrows in the Y Hyperspace and in the biplot generated by the interaction of the two coinertia axes. The modified coinertia analysis is included in Fig. 1.

Hodgkin's lymphoma of the thyroid in a woman with autoimmune thyroiditis / / Linfoma Hodgkin de tiroides en una mujer con tiroiditis autoinmune

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Predictive factors of achieving therapeutic goals of hypertriglyceridemia.

OBJECTIVES: The aim of this study was to ascertain the factors associated with non-achievement of triglyceride (TG) goals in a cohort of hypertriglyceridemic patients attending the lipid clinics of the Spanish Arteriosclerosis Society (LC-SAS). METHODS: Patients with high TG levels (>2.2 mmol/L; 200 mg/dL) were included in this multicenter, prospective, observational study and followed up for 1 year. The TG goal was ≤2.2 mmol/L (200 mg/dL). Main limitations of this study are that etiologic diagnosis of hypertriglyceridemia was not done under unified criteria and drug compliance was not evaluated. RESULTS: From 1394 patients initially included in the study, 929 (age range: 50 ± 12 years, 26% women) were followed up for 1 year; 523 patients (56%) failed to reach the TG target. These patients were younger, had a higher body mass index (BMI), were more frequently smokers, hypertensive and diabetic and had more severe dyslipidemia. They were also more sedentary, their diet was of poorer quality and they had higher alcohol consumption. The independent predictors of treatment failure were hypertriglyceridemia severity, low high density lipoprotein cholesterol (HDL-C), and high non-HDL-C, alcohol consumption and a raised BMI, while drug treatment had no predictive power. CONCLUSION: Independent predictors of failure to achieve hypertriglyceridemia treatment goals are inappropriate lifestyle, evidenced by insufficient weight loss, alcohol consumption and dyslipidemia severity.

Role of TNF in sickness behavior and allodynia during the acute phase of Chagas' disease.

Chagas disease, caused by the intracellular protozoan Trypanosoma cruzi, is associated with inflammation, discomfort and pain during the acute phase. The influence of TNF-α (tumor necrosis factor) in this disease outcome is controversial. In this way, the aim of this work was to determine the role of the TNF-α blocker etanercept in the pain, discomfort, and survival during the Chagas' acute phase of mice experimentally infected with a wild virulent strain of T. cruzi. The infection with this wild strain was responsible for a severe visceral inflammation and said parasite showed a tropism in peritoneal fluid cells. Etanercept was able to restore spontaneous vertical and horizontal activities during the second week after infection and to abolish mechanical allodynia during the first week after infection. Finally, etanercept delayed the mortality without any effect on the parasitemia rates. This is the first report that correlates sickness behavior and allodynia with TNF-α and suggests that this cytokine may play an important role in the physiopathology of the acute phase.

Induction of chagasic-like arrhythmias in the isolated beating hearts of healthy rats perfused with Trypanosoma cruzi-conditioned medium.

Chagas' myocardiopathy, caused by the intracellular protozoan Trypanosoma cruzi, is characterized by microvascular alterations, heart failure and arrhythmias. Ischemia and arrythmogenesis have been attributed to proteins shed by the parasite, although this has not been fully demonstrated. The aim of the present investigation was to study the effect of substances shed by T. cruzi on ischemia/reperfusion-induced arrhythmias. We performed a triple ischemia-reperfusion (I/R) protocol whereby the isolated beating rat hearts were perfused with either Vero-control or Vero T. cruzi-infected conditioned medium during the different stages of ischemia and subsequently reperfused with Tyrode's solution. ECG and heart rate were recorded during the entire experiment. We observed that triple I/R-induced bradycardia was associated with the generation of auricular-ventricular blockade during ischemia and non-sustained nodal and ventricular tachycardia during reperfusion. Interestingly, perfusion with Vero-infected medium produced a delay in the reperfusion-induced recovery of heart rate, increased the frequency of tachycardic events and induced ventricular fibrillation. These results suggest that the presence of parasite-shed substances in conditioned media enhances the arrhythmogenic effects that occur during the I/R protocol.

Induction of chagasic-like arrhythmias in the isolated beating hearts of healthy rats perfused with Trypanosoma cruzi-conditioned medium

Chagas' myocardiopathy, caused by the intracellular protozoan Trypanosoma cruzi, is characterized by microvascular alterations, heart failure and arrhythmias. Ischemia and arrythmogenesis have been attributed to proteins shed by the parasite, although this has not been fully demonstrated. The aim of the present investigation was to study the effect of substances shed by T. cruzi on ischemia/reperfusion-induced arrhythmias. We performed a triple ischemia-reperfusion (I/R) protocol whereby the isolated beating rat hearts were perfused with either Vero-control or Vero T. cruzi-infected conditioned medium during the different stages of ischemia and subsequently reperfused with Tyrode's solution. ECG and heart rate were recorded during the entire experiment. We observed that triple I/R-induced bradycardia was associated with the generation of auricular-ventricular blockade during ischemia and non-sustained nodal and ventricular tachycardia during reperfusion. Interestingly, perfusion with Vero-infected medium produced a delay in the reperfusion-induced recovery of heart rate, increased the frequency of tachycardic events and induced ventricular fibrillation. These results suggest that the presence of parasite-shed substances in conditioned media enhances the arrhythmogenic effects that occur during the I/R protocol.

Relation between lipoprotein subfractions and TSH levels in the cardiovascular risk among women with subclinical hypothyroidism.

OBJECTIVE: Subclinical hypothyroidism (SCH) is a common condition associated with increased cardiovascular risk. A standard treatment is yet to be established, as there is no consensus on the TSH cut-off values which should be used as indicators. Thus, the aim of this study was to assess cardiovascular risk in patients with SCH and to differentiate it according to TSH levels. DESIGN: This was an observational study conducted in an academic medical centre. PATIENTS: The study population consisted of 95 middle-aged women recently diagnosed with SCH and 65 euthyroid controls. MEASUREMENTS: We measured anthropometric parameters, lipid cardiovascular risk markers and lipoprotein subclasses of HDL and LDL. RESULTS: Patients with SCH exhibited a significant increase in triglycerides and atherogenic index of plasma and a significant reduction in HDL-cholesterol with respect to the control group after adjusted by age and BMI. A similar lipid profile was observed in both SCH groups. However, patients with TSH levels higher than 10 mIU/l showed a significant reduction in LDL particle size, which was associated with a higher prevalence of atherogenic pattern B. CONCLUSIONS: Our findings indicate that cardiovascular risk is affected in patients with TSH levels over 10 mIU/l, who have a lipid profile characteristic of atherogenic dyslipidemia.

Serum lipid responses to phytosterol-enriched milk in a moderate hypercholesterolemic population is not affected by apolipoprotein E polymorphism or diameter of low-density lipoprotein particles.

BACKGROUND/OBJECTIVES: The importance of both low-density lipoprotein cholesterol (LDLc) size and the apolipoprotein E (Apo E) in the atherogenic process is known, but there is little information with regard to the effect of phytosterols (PS) on these parameters. The aim of this study was to evaluate the influence of PS on lipid profile and LDLc size according to Apo E genotype. SUBJECTS/METHODS: This was a randomized parallel trial employing 75 mild-hypercholesterolemic subjects and consisting of two 3-month intervention phases. After 3 months of receiving a standard healthy diet, subjects were divided into two intervention groups: a diet group (n=34) and a diet+PS group (n=41) that received 2 g/day of PS. Total cholesterol (TC), triacylglycerols, LDLc, high-density lipoprotein cholesterol (HDLc), non-HDLc, Apo A-I and B-100, LDLc size and Apo E genotype were determined. RESULTS: Patients receiving PS exhibited a significant decrease in TC (5.1%), LDLc (8.1%), non-HDLc (7.4%) and Apo B-100/Apo A-I ratio (7.7%), but these effects did not depend on Apo E genotype. No significant changes were found in lipid profile according to Apo E genotype when patients following dietary recommendations were considered as a whole population or separately. No variations in LDLc size were observed in any of the intervention groups. CONCLUSION: The results of this study show that Apo E genotype does not have an impact on the lipid response to PS as a cholesterol-lowering agent in mild-hypercholesterolemic patients. Furthermore, the evidence obtained confirms that LDLc particle size is not modified when PS are added to a standard healthy diet.

Oxidative stress and endothelial dysfunction in cardiovascular disease: mitochondria-targeted therapeutics.

Functional impairment of endothelial activity (endothelial dysfunction) precedes the development of cardiovascular diseases (CVD). This condition is a result of a reduced bioavailability of nitric oxide (NO), a well known vasodilator, which is mainly due to increased NO degradation caused by its reaction with reactive oxygen species (ROS). Although there are several conditions that contribute independently to endothelial dysfunction, such as hyperglycemia, insulin resistance, hyperinsulinemia and dyslipidemia, increased oxidative stress seems to play a key role. In addition to their original pharmacological properties, drugs used clinically at present, including anti-hypertension reagents, angiotensin receptor blockers and anti-hyperlipidemic reagents such as statins, protect various organs via anti-oxidative stress mechanisms. Moreover, some substances with antioxidant properties, such as vitamin C or vitamin E, have been used to eradicate the oxidative stress associated with CVD. The results of the clinical trials employing anti-oxidative stress reagents in patients with CVD are contradictory, which could be a result of inadequate study design or selected targets. This review considers the process of endothelial dysfunction and CVD from a mitochondrial perspective and evaluates strategies currently under development for the targeted delivery of antioxidants or NO to mitochondria. It endorses the idea that selectively targeting specific antioxidants and NO donors to mitochondria is an effective strategy for modulating mitochondrial respiration and ROS production and protecting mitochondria against oxidative stress.