[Olmesartan-associated enteropathy: attention to an emerging iatrogenic phenomenon]. / Enteropatía asociada a olmesartán: atención a un fenómeno iatrogénico emergente.

Olmesartan is an angiotensin II type 1 receptor blocker commonly used in the treatment of hypertension. Several cases of sprue-like enteropathy associated with the use of this drug have been described which, even with important signs and limitations for the patient, present a full recovery after discontinuing the use of olmesartan. The case of a 64 year-old patient is presented, diagnosed with hypertension, under treatment with olmesartan-amlodipine, with chronic diarrhoea and villous atrophy on intestinal biopsies without diagnostic criteria for celiac disease and with complete remission after suspending discontinuing the use of olmesartan. Based on the clinical features presented by the case reported, the clinical and anatomopathological findings are described as well as the evolution of drug-induced enteropathy.

[Oxidative stress, diseases and antioxidant treatment]. / Estrés oxidativo, enfermedades y tratamientos antioxidantes.

Oxidation is a biochemical process of loss of electrons associated with another of reception called reduction. This process is capital for life, because it takes part in the production of cellular energy. Oxidative stress appears when oxidation is excessive. This reality is complex in all biological levels, and cannot be measured or defined by a single parameter. A great number of diseases have been related to oxidative stress and generation of free radicals. For this reason, antioxidant therapies and diets (such as mediterranean diet) rich or enriched with antioxidants seem to prevent or at least to attenuate the organic deterioration originated by an excessive oxidative stress.

Disección aórtica espontánea sin dolor torácico y con síntomatología neurológica / Spontaneous aortic dissection without thoracic pain and with neurological symptoms

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[Effect of losartan on human platelet activation by thromboxane A2]. / Efecto del losartán sobre la activación de plaquetas humanaspor tromboxano A2.

INTRODUCTION AND OBJECTIVES: Previous studies have demonstrated that losartan, an AT-1 receptor antagonist of angiotensin II (Ang II) could block the receptor of thromboxane A2 (TXA2) in the vascular wall. The aim of the present study was to assess the effect of losartan on human platelet activation. MATERIALS AND METHODS: Platelets were obtained from 15 healthy men between the age 26 and 40. Platelet activation was measured by changes in the light transmission of platelet-rich plasma stimulated by a synthetic TXA2 analogue, U46619 (5 x 10(-6) mol/l). RESULTS: The U46619-stimulated platelet aggregation was significantly inhibited by losartan in a dose-response manner. Only a high dose of EXP 3174 (5 10-5 mol/l), the in vivo active metabolite of losartan, was able to attenuate U46619-induced platelet activation. Captopril, an angiotensin I-converting inhibitor failed to modify U46619-induced platelet aggregation. Despite the platelets expressing AT-1 type receptors, of Ang II exogenous Ang II did not modify platelet aggregation induced by U46619. The binding of U46619 to platelets was competitively inhibited by losartan in dose-dependent manner. However, only a high dose of EXP 3174 reduced the binding of U46619. Captopril failed to modify the binding of U46619 to platelets. CONCLUSIONS: Losartan decreased platelet aggregation by a TXA2-dependent mechanism. EXP 3174 showed a lesser potency than losartan to reduce TXA2-platelet activation. Captopril and exogenous angiotensin II had no effect on human platelet activation. These results suggest that losartan reduced TXA2-dependent platelet activation independently of the blockade of AT-1 receptors.

[The effect of triflusal on human platelet aggregation and secretion: the role of nitric oxide]. / Efecto del triflusal sobre la agregación y secreción de las plaquetas humanas: papel del óxido nítrico.

INTRODUCTION AND AIMS: The thrombotic process is a multicellular phenomenon in which not only platelets are involved but also neutrophils are involved. Recent in vitro studies performed in our laboratory have demonstrated that triflusal reduced platelet aggregation by stimulating nitric oxide (NO) production by neutrophils. The aim of the present study was to evaluate whether the in vivo treatment with triflusal could also modify the ability of neutrophils to produce NO. Furthermore, the role of NO released by neutrophils on platelet aggregation and secretion was also tested. METHODS: The study was performed in 12 healthy volunteers of 32 +/- 6 years of age. The volunteers were treated with triflusal (600 mg/day) for 5 days and platelets and neutrophils were isolated before and after treatment. The ability of neutrophils to produce NO and the capacity of inhibiting platelet aggregation and secretion of transforming growth factor-beta (TGF-beta) were assessed. RESULTS: After the treatment with triflusal we obtained the following results: a) an increase in NO production by neutrophils; b) potentiation of the inhibition of platelet aggregation by neutrophils, an effect that was reverted by incubating neutrophils with an L-arginine antagonist, L-NAME, and c) the presence of neutrophils reduced the release of TGF-beta by platelets measured as index of platelet secretion by a NO-independent mechanism. CONCLUSIONS: Triflusal (600 mg/day/5 days) stimulated NO production by neutrophils. After the treatment with triflusal, neutrophils inhibited both platelet aggregation and secretion. The antiaggregating effect of neutrophils was an NO-dependent mechanism while the inhibition of platelet secretion mediated by neutrophils after the treatment with triflusal was an NO-independent mechanism.

Evidence that an endothelial cytosolic protein binds to the 3'-untranslated region of endothelial nitric oxide synthase mRNA.

Changes in the endothelial nitric oxide synthase (eNOS) expression could be involved in the endothelium-dependent vasorelaxing dysfunction associated with cardiovascular diseases. We have recently demonstrated the existence of endothelial cytosolic proteins that bind to the 3'-untranslated region (3'-UTR) of eNOS mRNA and could be involved in eNOS mRNA stabilization. In the present work, we have characterized the cytosolic proteins that bind to 3'-UTR eNOS mRNA. An endothelial cytosolic protein (MW 60-kD) specifically bound to 3'-UTR eNOS mRNA as determined by a cross-linking assay followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The endothelial cytosolic protein recognized a cytidine (C)-rich region within 3'-UTR eNOS mRNA. Furthermore, tumor necrosis factor-alpha (TNF-alpha) increased the level of the 60-kD endothelial cytosolic protein. In addition, TNF-alpha reduced eNOS mRNA levels and this was prevented by coincubation with cycloheximide. Cycloheximide also prevented the binding activity of the endothelial cytosolic protein to 3'-UTR eNOS mRNA. In summary, these data suggest that a 60-kD endothelial cytosolic protein binds to 3'-UTR eNOS mRNA. TNF-alpha increased the 60-kD protein levels. Cycloheximide prevented the binding activity of the cytosolic protein to 3'-UTR eNOS mRNA related to TNF-alpha; this effect was associated with greater eNOS mRNA levels. Further specific studies are needed to determine the involvement of this 60-kD endothelial cytosolic protein in the regulation of eNOS mRNA stabilization and in the endothelial dysfunction associated with cardiovascular diseases.

[Drug prescription in internal medicine: an analysis of the influencing factors]. / Prescripción de medicamentos en medicina interna: análisis de los factores de influencia.

BACKGROUND: The amount and quality of drugs prescribed after hospitalization in Internal Medicine and the factors which influence them have been rarely evaluated in Spain. MATERIAL AND METHODS: We study prospectively drugs prescribed in patients hospitalized in Internal Medicine analyzing amount of drugs before admission (BAD), on discharge (DD), end drugs after temporal drugs were removed (ED), drugs prescribed as chronic treatment (CTD), symptomatic drugs (SD), acute-use drugs (AUD) and low therapeutic utility drugs (LTUD). We also evaluated the sort of drugs and the factors implicated in increase or decrease of prescription volume. RESULTS: Two hundred and eighty-five patients were evaluated [164 males, 121 females, mean age 68.08 (SD 15.27)]. They had mean BAD 3.42(SD 2.67)7 DD 3.92 (SD 2.36) (p < 0.001) and ED 3.65 (SD 2.30) (No differences with BAD). The amount of drugs were higher in patients 65 years old and elder (p < 0.001). LTUD were decreased from 62(22%) patients on admission to 21 (7%) on discharge (p < 0.001). Compounded drugs were reduced from 36 (13%) patients to 17 (6%) (p < 0.05). Age older 65, length of stay greater 7 days, need for intravenous administration of drugs, comorbidities and complications during hospitalization all caused increase in prescription volume on discharge. Logistic-regression analysis showed that CTD and AUD were the main causes of increase of drugs while BAD and LTUD were protective. Drugs reduced in higher proportion were mucolytics (p < 0.005) drugs to treat plant-based hyperplasia benign of prostate (p < 0.05), brain vasodilators (p < 0.001) and peripheral vasodilators (p < 0.01). CONCLUSIONS: Hospitalization in Internal Medicine results in an increase of prescription volume though it is short-term. The higher number of drugs is accumulated in elderly. Factors implicated in increasing are length of stay, need for intravascular access, complications during inpatient, drugs to treat acute diseases and chronic use drugs. Low therapeutic utility drugs are used before admission in outpatients.

[Etiological study and diagnosis of anemia in adults over 60 years of age]. / Estudio etiológico y diagnóstico de anemias en adultos de mayores de 60 años.

PURPOSE: Anaemia especially iron deficiency anaemia (IDA) is a worldwide health problem and the most frequent nutritional lack in developing countries. The epidemiology of anaemia in hospitalized patients in Internal Wards is not well-known. PATIENTS AND METHODS: On a retrospective basis we studied 105 patients with haemoglobin levels below 115 g/L. Symptoms, type of anaemia, causing disease, diagnostic procedures, pathologic findings and transfusional schedule were analyzed. RESULTS: Mean haemoglobin was 77.8 (SD 17.9) g/L. Anaemia degree was deeper in women (p < 0.05) and IDA comparatively with chronic disease (CDA) (p < 0.01) and it did not show relation with therapeutic agents which potentially induce anaemia. IDA was the most frequent followed by haemorrhagic anaemia (HA) and CDA. The diagnostic procedure which discovered an underlying disease in most of the cases was upper digestive tract endoscopy, and CDA needed the highest number of diagnostic procedures. There was not relationship between the sort of anaemia and symptoms due to upper digestive tract and endoscopic findings, however low digestive tract symptoms (bleeding and abnormal finger rectal examination) and pathologic findings in colonoscopy had a straight relation (p < 0.05). CONCLUSIONS: IDA is the anaemia most frequently diagnosed in an Internal Medicine Department followed by HA and ACD. Clinical symptoms and the type of anaemia have poor correlation. In IDA upper digestive endoscopy as well as lower digestive tract examination is mandatory. We propose colonoscopy in patients aged more than 50-years whereas barium enema could be employed in younger people.

Comparison of in vitro effects of triflusal and acetysalicylic acid on nitric oxide synthesis by human neutrophils.

Recent studies have suggested that the protective anti-ischemic effects of acetylsalicylic acid are stronger than the inhibition of platelet thromboxane A2 synthesis. Since ischemic events still occur in acetylsalicylic acid-treated patients, the development of new drugs with more powerful protective effects is needed. We compared the effects of a new platelet antiaggregating drug, 2-acetoxy-4-trifluoromethyl-benzoic acid (triflusal) and of acetylsalicylic acid on the interaction between human neutrophils and platelets, examining the capability of neutrophils to generate nitric oxide (NO). Triflusal, in the presence of neutrophils, showed a greater antiplatelet potency than acetylsalicylic acid to inhibit thrombin-induced platelet activation. Significant stimulation of NO-mediated mechanisms in the presence of acetylsalicylic acid or triflusal was demonstrated by the following findings: (1) increased metabolism of arginine to citrulline, (2) increase of cGMP in the platelet/neutrophil system and (3) the inhibitory action of the L-arginine (L-Arg) competitive analogue, NG-nitro-L-arginine-methyl ester (L-NAME), which was reversed by L-Arg. Triflusal increased the stimulation of NO synthesis by neutrophils more than did of acetylsalicylic acid. The main metabolite of triflusal, 2-hydroxy-4-trifluoromethylbenzoic acid (HTB), alone or in combination with acetylsalicylic acid, did not modify NO production by neutrophils. Therefore, the whole molecule of triflusal is needed to stimulate NO production by neutrophils. Our results show that, in the presence of neutrophils, triflusal exerts an antiplatelet effect greater than that of acetylsalicylic acid, demonstrating a more powerful stimulation of the NO/cGMP system. The present results indicate that it is possible to develop new and more potent acetylsalicylic acid-related antiplatelet drugs for the prevention of the myocardial ischemic/reperfusion processes.