Neurohormonal activation induces intracellular iron deficiency and mitochondrial dysfunction in cardiac cells.

BACKGROUND: Iron deficiency (ID) is common in patients with heart failure (HF) and is associated with poor outcomes, yet its role in the pathophysiology of HF is not well-defined. We sought to determine the consequences of HF neurohormonal activation in iron homeostasis and mitochondrial function in cardiac cells. METHODS: HF was induced in C57BL/6 mice by using isoproterenol osmotic pumps and embryonic rat heart-derived H9c2 cells were subsequently challenged with Angiotensin II and/or Norepinephrine. The expression of several genes and proteins related to intracellular iron metabolism were assessed by Real time-PCR and immunoblotting, respectively. The intracellular iron levels were also determined. Mitochondrial function was analyzed by studying the mitochondrial membrane potential, the accumulation of radical oxygen species (ROS) and the adenosine triphosphate (ATP) production. RESULTS: Hearts from isoproterenol-stimulated mice showed a decreased in both mRNA and protein levels of iron regulatory proteins, transferrin receptor 1, ferroportin 1 and hepcidin compared to control mice. Furthermore, mitoferrin 2 and mitochondrial ferritin were also downregulated in the hearts from HF mice. Similar data regarding these key iron regulatory molecules were found in the H9c2 cells challenged with neurohormonal stimuli. Accordingly, a depletion of intracellular iron levels was found in the stimulated cells compared to non-stimulated cells, as well as in the hearts from the isoproterenol-induced HF mice. Finally, neurohormonal activation impaired mitochondrial function as indicated by the accumulation of ROS, the impaired mitochondrial membrane potential and the decrease in the ATP levels in the cardiac cells. CONCLUSIONS: HF characteristic neurohormonal activation induced changes in the regulation of key molecules involved in iron homeostasis, reduced intracellular iron levels and impaired mitochondrial function. The current results suggest that iron could be involved in the pathophysiology of HF.

Study of factors that influence the outcome of 131I treatment in hyperthyroidism secondary to nodular goitre. / Estudio de los factores que influyen en el resultado del tratamiento con 131I en el hipertiroidismo por bocio nodular.

OBJECTIVE: To assess the outcome after 131I treatment in patients with multinodular (MNG) and nodular toxic goitre (NTG) according to the administered dose and other factors related to the patient, pathology, or previous treatments. MATERIAL AND METHODS: A retrospective study was conducted on 108 patients (67 MNG and 41 NTG) treated in our department, with a follow-up period of at least 2 years. Development of hypothyroidism and treatment failure were evaluated along with their relationship with the administered dose and other factors such as age, sex, grade of hyperthyroidism, type of goitre, presence of autoimmunity, or previous antithyroid medication. RESULTS: More than one-third (36.9%) of MNG patients, and even higher proportion of NTG patients (51.2%) developed non-transient hypothyroidism, particularly in those receiving 740MBq (66.7%). No relationship was found with any other variable. The development of early hypothyroidism (before one year) was also not related to any variable. Treatment failure was not related to the dose, but in MNG there was a relationship with male gender, presence of autoimmunity, or previous antithyroid drugs use. CONCLUSIONS: The high rate of hypothyroidism obtained with high doses of 131I in hyperthyroidism secondary to nodular goitre treatment suggests that lower doses might be sufficient to control the disease without an increase in treatment failures. Only patients with positive autoimmunity, in previous anti-thyroid medication, and perhaps male gender in MNG might be given higher doses, as the failure rate increases, but further studies are required.

[Carbapenem resistance in Pseudomonas aeruginosa isolated from urine cultures: prevalence and risk factors]. / Resistencia a carbapenemas en Pseudomonas aeruginosa aisladas en urocultivos: prevalencia y factores de riesgo.

OBJECTIVE: Pseudomonas aeruginosa is a non-fermentative gram-negative bacillus with a great ability to develop resistance to multiple antibiotics, including carbapenems, which is a growing problem worldwide. The aim of this study was to analyse the prevalence of carbapenem-resistant P. aeruginosa (CRPA) in urine cultures and to determine the risk factors associated with the development of carbapanem resistance. METHODS: Positive urine cultures to P. aeruginosa between September 2012 and September 2014 were identified. We excluded repetitive cultures from the same patient. We created a database with different variables, including antimicrobial resistance. The prevalence of carbapenem resistance and the risk factors for growth of CRPA were analysed. RESULTS: Ninety-one patients with positive urine cultures to P. aeruginosa were included. The prevalence of CRPA was 22%. The risk factors to CRPA infection in the univariate analysis were: congestive heart failure (p=0.02), previous treatment with ampicillin (p=0.04), meropenem (p=0.04), piperacillin-tazobactam (p=0.01), trimethoprim-sulfamethoxazole (p= 0.01) and previous treatment with more than one antibiotic (p<0.01). Only congestive heart failure (p<0.01) and previous treatment with more than one antibiotic (p<0.01) showed statistically significant differences in the multivariate analysis. CONCLUSIONS: The prevalence of CRPA in urine cultures is high in our population. We should assess the presence of risk factors as previous treatment with more than one antibiotic or comorbidities such as heart failure, in order to select an appropriate empirical treatment in patients with severe urinary tract infections.

Rationale and study design of the RESERVOIR trial: a randomized trial comparing reservoir-based polymer-free amphilimus-eluting stents versus everolimus-eluting stents with durable polymer in patients with diabetes mellitus.

BACKGROUND: Patients with diabetes mellitus (DM) remain at high risk for stent restenosis and adverse cardiovascular events in the drug-eluting stent era. The amphilimus-eluting stent (AES) is a third generation reservoir-based polymer-free drug-eluting stent that has shown promising preliminary results in patients with DM. It has been suggested that the formulation of the drug with fatty acids could not only modulate the drug release in a timely manner but also achieve convenient levels of drug concentration in diabetic cardiac cells. The aim of this trial is to assess the efficacy of the AES in patients with DM compared with the cobalt chromium everolimus-eluting stent with non-erodible polymer (EES). STUDY DESIGN: This is an investigator-initiated, multicenter, randomized clinical trial, performed in patients with DM. A total of 112 diabetic patients receiving glucose-lowering agents and requiring percutaneous revascularization of a de novo lesion will be randomized in a 1:1 fashion to receive AES or EES. The primary endpoint is the neointimal volume obstruction at 9 months, evaluated by optical coherence tomography. Secondary endpoints will include strut coverage, angiographic in-stent late loss and clinical endpoints such as target vessel revascularization or probable/definite stent thrombosis. This study completed the inclusion in October 2013. CONCLUSIONS: The RESERVOIR trial is an investigator-initiated trial that will evaluate whether the polymer-free AES is not inferior to the EES inhibiting the neointimal hyperplasia in patients with DM. These results are also expected to improve our knowledge of the neointimal healing process in this population (Clinicaltrials.gov number NCT01710748).

Antiplatelet therapy: new pharmacological agents and changing paradigms.

Recurrent atherothrombotic events in patients with acute coronary syndromes (ACS) and/or those undergoing percutaneous coronary intervention (PCI) are essentially platelet-driven processes, underscoring the need for effective pharmacological platelet inhibition. Dual antiplatelet therapy with aspirin and clopidogrel has been, for over a decade, the mainstay of antiplatelet management in ACS/PCI. However, atherothrombotic events continue to occur in a relevant proportion of subjects despite the benefit of this combination, which has led to the clinical development of newer and more potent antiplatelet drugs. Two of these, prasugrel and ticagrelor, have been recently approved for clinical use. The scope of this manuscript is to provide an up-to-date overview on new antiplatelet drugs in the setting of ACS and PCI, including the most recent advances on newly approved agents as well as on emerging compounds in clinical development.

Enfermedad de Behçet asociada a déficit de corticotropina / Behçet disease with isolated acth deficiency

Presentamos un paciente con enfermedad de Behçet de larga evolución, con predominio de manifestaciones neurológicas, que ingresó por insuficiencia suprarrenal, en el que se demostró déficit aislado de corticotropina (DAACTH). El DAACTH es una característica típica de las hipofisitis y se ha descrito en asociación con múltiples enfermedades autoinmunitarias; sin embargo, la afección hipotálamo-hipofisaria en la enfermedad de Behçet es excepcional. Revisamos los casos publicados y los posibles mecanismos patogénicos de esta asociación hasta ahora no descrita (AU)

We report a case of a patient with longstanding Behçet disease, with neurological symptoms predominantly, who became hospitalized for adrenal insufficiency, caused by isolated deficiency of corticotropin (DAACTH). DAACTH is a typical characteristic of hypophysitis, reported in association with many autoimmune diseases. Nevertheless, hypothalamic-pituitary injury in Behçet disease is exceptional. We review the literature and possible mechanisms of this association until now not reported (AU)

Síndrome Post-polio / Clinical features and electromyographic variables in patients with post-polio syndrome

La primera descripción del síndrome de post-polio fue publicada en la literatura francesa en 1875, pero se reconoce recién esta entidad a partir de la dúcada de los 80. Su inicio es aproximadamente 30 años después del episodio agudo a través de distintos síntomas: fatiga, debilidad de músculos previamente afectados y previamente no afectados, dolor, intolerancia al frío, atrofia muscular y nuevos problemas de la vida diaria. Se estudiaron 12 pacientes que presentaron nueva sintomatología, principalmente debilidad muscular y dolor en distintos grupos musculares, ya sea por desuso o por un esfuerzo exagerado y dolor en las articulaciones

Síndrome Post-polio / Clinical features and electromyographic variables in patients with post-polio syndrome

La primera descripción del síndrome de post-polio fue publicada en la literatura francesa en 1875, pero se reconoce recién esta entidad a partir de la dúcada de los 80. Su inicio es aproximadamente 30 años después del episodio agudo a través de distintos síntomas: fatiga, debilidad de músculos previamente afectados y previamente no afectados, dolor, intolerancia al frío, atrofia muscular y nuevos problemas de la vida diaria. Se estudiaron 12 pacientes que presentaron nueva sintomatología, principalmente debilidad muscular y dolor en distintos grupos musculares, ya sea por desuso o por un esfuerzo exagerado y dolor en las articulaciones

[Osteoarticular infections caused by Streptococcus agalactiae. Report of 4 cases]. / Infecciones osteoarticulares por Streptococcus agalactiae. Aportación de 4 casos.

BACKGROUND: Streptococcus agalactiae (group B streptococcus) is a rare etiology of osteoarticular infection in adults. In a literature review (Medline-Embase plus) up until may 1994, we have found only 51 cases. In most patients, diabetes mellitus, liver disease or long-term steroid therapy were documented. METHODS: Four adult patients with osteoarticular infection due to S. agalactiae from two Galician hospitals were studied from January 1988 to October 1994: prepatellar bursitis (one case), septic monoarthritis (2 cases) and psoas abscess associated to cervical spondylodiscitis and oligoarthritis (left sternoclavicular and left hip joints). RESULTS: In the first patient, a young woman with prepatellar bursitis, a previous local trauma was recorded. The second case, a man with septic arthritis of right knee, had degenerative disease of the knees and a prostatic adenocarcinoma. In the third patient, a diabetic woman with septic arthritis of the left shoulder, vulvovaginitis due to Candida albicans was found. The last patient suffered vertebral osteomyelitis of the cervical spine (C3-C4), arthritis of the left sternoclavicular and hip joints and abscess of the ipsilateral psoas. The evolution was favourable in the four cases. CONCLUSIONS: Although uncommon, osteomyelitis and arthritis caused by group B streptococcus should be considered as opportunistic pathogen in adults with debilitating conditions. Early recognition and prompt institution of adequate therapy can help avoid joint destruction and severe complications.

Case report 866. Pseudotumor of the muscle associated with necrotizing vasculitis of medium- and small-sized arteries and chronic myositis.

A case of polymyositis and localized vasculitis presenting as a muscular pseudotumor of a lower extremity and periostitis several years after the onset of symptoms was reported and the MRI characteristics were described. This imaging modality demonstrated muscle signal abnormalities in several muscle groups and was useful in ruling out the presence of a mass and fatty degeneration of the muscle. The ability of the STIR sequence (Fig. 3D) to show muscle abnormalities and to allow fatty infiltration or degeneration to be ruled out has not been reported before in patients with vasculitic muscle involvement.

Mielinolisis central pontina / Central pontine myelinolysis

Se presenta un paciente de 23 años con quemaduras de 2do. y 3er. grado que comprometieron el 45%de la superficie corporal. A los 25 días de evolución se instaló un deterioro del nivel de conciencia, con somnoliencia asociada a hiperosmolaridad, hiperglucemia (341 mosm/kg; 210 mg.dl) e hipernatremia (151 mEq/l) sin signos de IRA. Corregido en 48 hs. el desequilibrio osmótico por aporte de fluidos, apareció luego un cuadro de obnubilación con tetraparesia que se completó en 24 hs. A los 24 días de ésta, una TC mostró una lesión hipodensa compatible con mielinolisis central pontina. Se concluye que la hiperosmolaridad asociada a una pérdida de osmoles idiogénicos, típico de estados hipercatabólicos, es la responsable de la mielinolisis central pontina

Mielinolisis central pontina / Central pontine myelinolysis

Se presenta un paciente de 23 años con quemaduras de 2do. y 3er. grado que comprometieron el 45%de la superficie corporal. A los 25 días de evolución se instaló un deterioro del nivel de conciencia, con somnoliencia asociada a hiperosmolaridad, hiperglucemia (341 mosm/kg; 210 mg.dl) e hipernatremia (151 mEq/l) sin signos de IRA. Corregido en 48 hs. el desequilibrio osmótico por aporte de fluidos, apareció luego un cuadro de obnubilación con tetraparesia que se completó en 24 hs. A los 24 días de ésta, una TC mostró una lesión hipodensa compatible con mielinolisis central pontina. Se concluye que la hiperosmolaridad asociada a una pérdida de osmoles idiogénicos, típico de estados hipercatabólicos, es la responsable de la mielinolisis central pontina

Parkinsonismo juvenil: a propósito de 18 casos / Juvenile parkinsonism: apropos of 18 cases

Se acepta como variante juvenil de la enfermedad de Parkinson a aquellos casos en que los trastornos que la caracterizan se instalan antes de los 40 años de edad. se comuncian 18 pacientes cuya edad al iniciarse el padecimiento oscilaba entre 15 y 34 años, y que reunían las condiciones para ser incorporados a este estudio y que tuvieron un seguimiento de 9 a 17 años. Se efectúa en función de los hallazgos familiares, clínicos, evolutivos y terapéuticos observados, una revisión de la literatura al respecto coincidiendo, al menos parcialment en rasgos que singularizan a esta particular forma de parkinsonismo. Aparentemente el deterioro de la eficacia del tratamiento con L-Dopa en estos pacientes es más lento que en las formas preseniles y estaría relacionado a la duración de la enfermedad y no al tiempo de la terapia