Avaliação da tolerabilidade do micofenolato sódico com revestimento entérico versus micofenolato mofetil em receptores de transplante renal / Evaluation of tolerability of enteric-coated mycophenolate sodium versus mycophenolate mofetil in de novo renal transplantation

ResumoIntrodução:O micofenolato mofetil (MMF), pró-droga do ácido micofenólico (MPA), é um tratamento imunossupressor eficaz na profilaxia da rejeição aguda, mas associado a eventos adversos gastrointestinais. O micofenolato sódico (MPS) com revestimento entérico foi desenvolvido com a intenção de reduzir tais eventos associados ao MPA.Objetivo:Avaliar a tolerabilidade de EC-MPS e MMF em receptores de transplante renal.Métodos:Estudo retrospectivo, multicêntrico, com pacientes submetidos a transplante renal entre 07/01/2004 e 31/07/2007 em 18 centros brasileiros.Resultados:1380 pacientes incluídos, 702 receberam EC-MPS e 678 receberam MMF. A idade média de 42,3 anos, 60% masculino e 62,5% de etnia caucasiana. A incidência de eventos avaliados no desfecho composto de eficácia não foi diferente entre os grupos ao final de 24 meses de acompanhamento (22,9% para EC-MPS versus 19,9% para MMF, p = 0,203). Os pacientes tratados com EC-MPS apresentaram maior incidência de eventos adversos gastrointestinais comparados com os tratados com MMF (57,7% vs. 52,5%). Infecções virais foram mais frequentes no grupo EC-MPS (38,2%) comparado com MMF (32,6%). Não houve diferença nos valores médios tolerados no final do primeiro (1187 ± 344 mg vs. 1209 ± 426 mg, p = 0,294) e segundo ano (1172,3 ± 347mg vs. 1197,4 ± 430,6 mg, p = 0,241) pós-transplante.Conclusão:Não houve diferença estatística na incidência de rejeição aguda, função tardia e eventos gastrointestinais entre os tratamentos. A dose média tolerada de MPA foi semelhante entre os grupos, mas pacientes tratados com MMF foram submetidos a mais reduções de doses e descontinuações do tratamento.

AbstractIntroduction:Mycophenolate mofetil (MMF), pro-drug mycophenolic acid (MPA) is an immunosuppressive effective in the prophylaxis of acute rejection, but associated with gastrointestinal adverse events. Mycophenolate sodium (MPS) with enteric coating was developed with intention of reducing such gastrointestinal adverse events associated with MPA.Objective:To evaluate the tolerability of EC-MPS and MMF in renal transplant recipients.Methods:Retrospective, multicenter study, included 1380 patients who underwent a transplant between 07/01/2004 and 31/07/2007 in 18 Brazilian centers.Results1380 patients enrolled, 702 received EC-MPS and 678 received MMF. The average age of patients was 42.3 years, 60% were male and 62.5% of Caucasian ethnicity. The incidence of events evaluated in the composite endpoint of efficacy was not different between groups at the end of 24 months follow-up (22.9% for EC-MPS to MMF versus19.9%, p = 0.203). Patients treated with EC-MPS had a higher incidence of gastrointestinal adverse events compared to those treated with MMF (57.7%vs. 52.5%), but there was no statistical difference between groups. Viral infections were more frequent in the EC-MPS group (38.2%) compared with MMF (32.6%). There was no difference in mean tolerated dose after the first (1187 ± 344vs. 1209 ± 426 mg, p = 0.294) and second year (1172.3 ± 347 mgvs. 1197.4 ± 430.6 mg, p = 0.241) after transplantation.Conclusion:There was no statistical difference in the incidence of acute rejection, delayed graft function and gastrointestinal events among treatments. The average tolerated dose of MPA was similar between groups; however, patients treated with MMF underwent more dose reductions and discontinuations of treatment.

Comparison of Acarbose and Voglibose in Diabetes Patients Who Are Inadequately Controlled with Basal Insulin Treatment: Randomized, Parallel, Open-Label, Active-Controlled Study

We studied the efficacy and safety of acarbose in comparison with voglibose in type 2 diabetes patients whose blood glucose levels were inadequately controlled with basal insulin alone or in combination with metformin (or a sulfonylurea). This study was a 24-week prospective, open-label, randomized, active-controlled multi-center study. Participants were randomized to receive either acarbose (n=59, 300 mg/day) or voglibose (n=62, 0.9 mg/day). The mean HbA1c at week 24 was significantly decreased approximately 0.7% from baseline in both acarbose (from 8.43% +/- 0.71% to 7.71% +/- 0.93%) and voglibose groups (from 8.38% +/- 0.73% to 7.68% +/- 0.94%). The mean fasting plasma glucose level and self-monitoring of blood glucose data from 1 hr before and after each meal were significantly decreased at week 24 in comparison to baseline in both groups. The levels 1 hr after dinner at week 24 were significantly decreased in the acarbose group (from 233.54 +/- 69.38 to 176.80 +/- 46.63 mg/dL) compared with the voglibose group (from 224.18 +/- 70.07 to 193.01 +/- 55.39 mg/dL). In conclusion, both acarbose and voglibose are efficacious and safe in patients with type 2 diabetes who are inadequately controlled with basal insulin. (ClinicalTrials.gov number, NCT00970528)

Chemotherapy induced liver abnormalities: an imaging perspective

Treating patients undergoing chemotherapy who display findings of liver toxicity, requires a solid understanding of these medications. It is important for any clinician to have an index of suspicion for liver toxicity and be able to recognize it, even on imaging. Cancer chemotherapy has evolved, and newer medications that target cell biology have a different pattern of liver toxicity and may differ from the more traditional cytotoxic agents. There are several hepatic conditions that can result and keen clinical as well as radiographic recognition are paramount. Conditions such as sinusoidal obstructive syndrome, steatosis, and pseudocirrhosis are more commonly associated with chemotherapy. These conditions can display clinical signs of acute hepatitis, liver cirrhosis, and even liver failure. It is important to anticipate and recognize these adverse reactions and thus appropriate clinical action can be taken. Often times, patients with these liver manifestations can be managed with supportive therapies, and liver toxicity may resolve after discontinuation of chemotherapy.

Safe Re-administration of Tumor Necrosis Factor-alpha (TNFalpha) Inhibitors in Patients with Rheumatoid Arthritis or Ankylosing Spondylitis Who Developed Active Tuberculosis on Previous Anti-TNFalpha Therapy

There is no consensus on whether it is safe to re-administer tumor necrosis factor-alpha (TNFalpha) inhibitors in patients with rheumatoid arthritis (RA) or ankylosing spondylitis (AS) flared after withdrawal of TNFalpha inhibitors due to active tuberculosis (TB). We evaluated the safety of restarting anti-TNFalpha therapy in patients with TNFalpha-associated TB. We used data of 1,012 patients with RA or AS treated with TNFalpha inhibitors at Seoul St. Mary's Hospital between January 2003 and July 2013 to identify patients who developed active TB. Demographic and clinical data including the results of tuberculin skin tests (TST) and interferon-gamma releasing assays (IGRA) were collected. Fifteen patients developed active TB. Five cases were occurred in RA and 10 cases in AS. Nine of 15 patients had a negative TST or IGRA and 6 TST-positive patients had received prophylaxis prior to initiating anti-TNFalpha therapy. All patients discontinued TNFalpha inhibitors with starting the treatment of TB. Eight patients were re-administered TNFalpha inhibitors due to disease flares and promptly improved without recurrence of TB. TNFalpha inhibitors could be safely resumed after starting anti-TB regimen in patients with RA or AS.

El sistema renina angiotensina y el estrés oxidativo en un modelo experimental de preeclampsia en ratas / The renin angiotensin system and the oxidative stress in a animal model of preeclampsia in rats

La preeclampsia es un síndrome exclusivo de la gestación humana y responsable de una alta morbimortalidad perinatal, cuyas manifestaciones incluyen: hipertensión arterial, proteinuria y edema. Un mecanismo postulado en la fisiopatología de la preeclampsia, es la reducción de la perfusión placentaria y el desarrollo del síndrome clínico materno ocasionado por la liberación de factores placentarios que afectan la regulación de la presión arterial y la función renal. Uno de los factores que ocasiona el trastorno endotelial son las especies reactivas de oxígeno, el incremento de elementos vasoactivos, así como la disminución de agentes vasorelajantes como el óxido nítrico. Todas estas alteraciones vasculares conducen no sólo a la hipertensión sino también a la disfunción renal. Debido a la importancia del papel del óxido nítrico y su desregulación en la preeclampsia, en el presente trabajo se caracterizó un modelo experimental de preeclampsia que resulta de la inhibición de la síntesis de óxido nítrico mediante la administración de L-NAME a ratas preñadas y no preñadas. En el mismo se evaluó el estatus oxidativo y, el papel del sistema renina angiotensina en la contribución de la disfunción renal. Los resultados demuestran el papel primordial del óxido nítrico y su desregulación en este modelo de preeclampsia experimental. En efecto, se demostró que el tratamiento durante siete días con L-NAME incrementó la presión arterial media, aumentó la sensibilidad vascular, inhibió la actividad de la sintasa del óxido nítrico renal y redujo el guanilil monofosfato cíclico urinario. La disfunción endotelial renal en este modelo experimental se manifiesto por proteinuria, incremento de la creatinina plasmática, disminución de la excreción urinaria de sodio, potasio y creatinina, así como, evidencia morfológica de endoteliosis glomerular. Al caracterizar el papel de las enzimas antioxidantes renales se encontró una reducción significativa de la actividad de las mismas, y un incremento de la peroxidación lipídica asociada a una elevada concentración de agentes pro-oxidantes. Nuestro modelo experimental constituye una buena aproximación a la preeclampsia humana y no un efecto inespecífico del L-NAME, ya que aún cuando la inhibición crónica de la síntesis de óxido nítrico en ratas no preñadas induce un incremento de la presión arterial media, proteinuria, reducción de la actividad de la sintasa del óxido nítrico renal y de la excreción urinaria de guanilil monofosfato cíclico similar a las ratas preñadas, los efectos sobre la proteinuria, las acciones morfológicas renales, la excreción urinaria de sodio, potasio y creatinina, y sobre el sistema renina angiotensina son específicos de la preeclampsia experimental en ratas. Así, se demostró que en las ratas preñadas tratadas con L-NAME la actividad de la enzima convertidora de angiotensina plasmática, los niveles de renina plasmática, y la aldosterona amniótica se encuentran marcadamente disminuidos, cuando se comparan con las ratas preñadas normotensas. Estos hallazgos sugieren que la preeclampsia experimental se caracteriza por la supresión de los componentes circulantes del sistema renina angiotensina, que podrían ser responsables del desbalance entre los sistemas vasoconstrictores y vasodilatadores observados en la preeclampsia, así como de algunos de los signos de la preeclampsia, similar a lo que ocurre en la mujer embarazada hipertensa. Por otra parte, al evaluar la contribución del estrés oxidativo en el daño renal en la preeclampsia experimental, se demostró una disminución de la actividad de las enzimas antioxidantes renales. Asimismo, la disminución de la actividad de la glutatión peroxidasa plasmática y la tendencia a la reducción en la glutatión peroxidasa en el líquido amniótico, con el simultáneo incremento de los valores de las sustancias que reaccionan con el ácido tiobarbitúrico (TBARS) plasmático, sugiriéndose que la desregulación generalizada y renal está asociada a una baja protección oxidativa durante la preeclampsia, que favorece a la insuficiencia renal. El incremento temprano del estrés oxidativo placentario juega un papel fundamental en la disfunción endotelial generalizada y el daño renal en la preeclampsia. Debido a ello, nos planteamos que el tratamiento temprano con antioxidantes o con desacoplantes de la NAD (P) H oxidasa podría interrumpir el proceso de este síndrome. Efectivamente, el tratamiento crónico con un compuesto que mimetiza a la superóxido dismutasa, el tempol, o el desacoplante del ensamblaje de la NAD(P)H oxidasa (apocinina), fueron capaces de reducir significativamente la hipertensión inducida por el L-NAME. Igualmente, ambos compuestos fueron capaces de prevenir la proteinuria y la reducción de la actividad de las enzimas antioxidantes renales estudiadas. En conclusión, la preeclampsia experimental inducida por la inhibición crónica de la síntesis de óxido nítrico en ratas preñadas, reproduce los signos clásicos de la preeclampsia humana, y se acompaña de la desregulación del sistema renina angiotensina y de disfunción renal. Esto nos permite aseverar que este modelo experimental de preeclampsia constituye una buena aproximación a la preeclampsia humana. Se demuestra que el daño renal encontrado en este modelo experimental se asocia a una disminución de los mecanismos antioxidantes renales, que lleva a un incremento del estrés oxidativo, y a una reducción de la protección de la función renal. Estos resultados indican que la sobreproducción de especies reactivas de oxígeno tanto placentaria como renal, son causa fundamental de la disfunción endotelial generalizada y del daño renal. Finalmente, la inhibición del estrés oxidativo mediante el uso de agentes antioxidantes como el tempol o la apocinina, pudiese ser una de las posibles estrategias terapéuticas en el tratamiento de la hipertensión inducida por el embarazo humano y abre nuevos horizontes en el tratamiento de este síndrome.

Pantoprazole provides myocardial protection similar to ischemic preconditioning: experimental study of isolated hearts of rats / Pantoprazol oferece proteção miocárdica semelhante ao pré-condicionamento isquêmico: estudo em corações isolados de ratos

OBJECTIVE: To evaluate pantoprazole effect in the functional recovery of isolated hearts of rats, submitted to ischemia and reperfusion with and without ischemic preconditioning. METHODS: In four groups of eight Wistar breed rats, the hearts were removed after anesthesia and perfused with Krebs-Henseleit solution (95% O2, 5% CO2, 37ºC). GI, GII, GIII and GIV hearts were submitted to ischemia (20 min) and reperfusion (30 min). In GII and GIV, preconditioning was performed with 5 min of ischemia and 5 min of reperfusion before 20 min of the ischemia period induction. In GIII and GIV pantoprazole 100 mg was done before a 20 min-period of ischemia induction. Heart Rate (HR), Coronary Flow (CoF), Systolic Pressure (SP), +dP/dt and -dP/dt were registered before (t0) and after reperfusion (t30). Kruskal-Wallis (P<0.05) test was used. RESULTS: There were no differences (P>0.05) between groups among HR and CoF values. Differences occurred between groups, I and II, III and IV at t30 with SP reduced for 32% mean value in GI, 65% GII, 65% GIII, and 73% GIV; The t30 + dP/dtmax were 34% in GI, 61% GII, 63% GIII and 72% GIV. The t30 -dP/dtmax were GI 28%, GII 63%, GIII 75 % and GIV 75%; (P<0.05). There were no significant differences in the SP, +dP/dtmax, and -dP/dtmax between Groups II, III and IV results. CONCLUSIONS: The administration of pantoprazole before induction of ischemia significantly protected the myocardial functional recovery with the results of SP, + dP / dtmax and dP/dtmax similar to the ischemic preconditioning against ischemia-reperfusion.

OBJETIVO: Avaliar o efeito do pantoprazol na recuperação funcional de corações isolados de ratos submetidos à isquemia e reperfusão com e sem pré-condicionamento isquêmico. MÉTODOS: Em quatro grupos de oito ratos Wistar, após anestesia os corações foram removidos e perfundidos com Krebs-Henseleit (95% O2, 5% CO2, 37ºC). Os corações de GI, GII, GIII e GIV foram submetidos a 20' de isquemia e 30'de reperfusão. Em GII e GIV realizou-se pré condicionamento com 5' de isquemia e 5' de reperfusão antes dos 20' de isquemia. Em GIII e GIV, pantoprazol 100mcg foram injetados imediatamente antes dos 20' de isquemia. Frequência cardíaca (FC), Fluxo Coronariano (FCo), Pressão Sistólica (PS), + dP/dt e -dP/dt foram registrados em (T0) e (t30). Estatística: Kruskal-Wallis (P <0,05). RESULTADOS: Não houve diferenças (P> 0,05) entre grupos nos valores de FC e de CFo. Diferenças (P <0,05) ocorreram entre GI e GII, GIII e GIV, com PS t30 reduzida para 32% GI, 65% GII, 65% GIII e 73% GIV. Em t30 + dP/dtmax 34% GI, 61% GII, 63% GIII e 72% GIV. A -dP/dtmax t30 GI 28%, GII 63%, GIII 75% e GIV 75%. Não houve diferença estatística (P< 0,05) nos valores de PS, +dP/dtmax e -dP/dtmax entre os GII, GIII e GIV. CONCLUSÕES: A administração do pantoprazol antes da indução da isquemia protegeu significativamente a recuperação funcional miocárdica com resultados de SP, +dP/ dtmax e -dP/dtmax semelhantes aos do pré-condicionamento isquêmico contra lesão de isquemia-reperfusão.

Drug Fever Due to Piperacillin/Tazobactam Loaded into Bone Cement

Although drug fever may develop after administration of the drug by various routes, it has not been reported with antibiotic-loaded bone cement. Here, a case of drug fever induced by piperacillin/tazobactam loaded into bone cement is reported. A 72-yr-old woman presented with fever that developed two weeks after insertion of bone cement loaded with antibiotics including piperacillin/tazobactam into the knee joint for infectious arthritis. The fever was associated with a skin rash and blood eosinophilia. The work-up of the fever excluded several causes. Drug provocation test demonstrated that the piperacillin/tazobactam, which had been loaded in the bone cement, was the cause of the fever. The findings of this case suggest that drug fever can be induced by any drug placed and released continuously within the body. Therefore, the evaluation for possible drug fever should include all drugs the patient has been exposed to regardless of the route of administration.

Laboratory diagnosis of late-onset male hypogonadism andropause / Diagnóstico laboratorial do hipogonadismo masculino tardio (andropausa)

OBJECTIVES: To evaluate which factors influence the laboratorial diagnosis of late-onset male hypogonadism (LOH). METHODS: Total testosterone (TT), SHBG and albumin were measured in 216 men aged 52-84 years. The laboratorial definition of LOH was two values of calculated free testosterone (cFT) <6.5 ng/dl, according to Vermeulen's formula. RESULTS: At the first blood test, cFT was <6.5 ng/dl in 27 percent of the men. Laboratorial LOH (confirmed by two tests) was present in 19 percent, but TT levels were low in only 4.1 percent. Age influenced TT (p=0.0051) as well as BMI; 23.5 percent of patients > 70 years and 38.9 percent of the obese men who had TT within the reference range were, in fact, hypogonadal. CONCLUSION: Especially in obese men and in those > 70 years old, SHBG dosage is important to calculate FT levels and diagnose hypogonadism.

OBJETIVOS: Avaliar os fatores que influenciam o diagnóstico laboratorial do hipogonadismo masculino tardio. MÉTODOS: Avaliamos 216 homens entre 52 e 84 anos. O diagnóstico laboratorial foi definido como dois valores de testosterona livre calculada (TLC) <6,5 ng/dl, segundo a fórmula de Vermeulen, a partir das dosagens de testosterona total (TT), SHBG e albumina. RESULTADOS: Na primeira dosagem, a TLC foi <6.5 ng/dl em 27 por cento da amostra. Hipogonadismo laboratorial (confirmado por duas dosagens) esteve presente em 19 por cento, no entanto a TT foi baixa em apenas 4.1 por cento dos homens. A idade influenciou a TT (p=0.0051) bem como o IMC; 23,5 por cento dos homens > 70 anos e 38,9 por cento dos obesos com TT dentro dos níveis de referência eram, na verdade, hipogonádicos. CONCLUSÃO: Especialmente em homens obesos e nos > 70 anos a dosagem de SHBG é importante para calcular TL e diagnosticar o hipogonadismo.

Drug-induced thyroid disorders.

Disorders of thyroid hormone metabolism are commonly encountered in clinical practice. Apart from conditions affecting the thyroid gland, thyroid hormone homeostasis may be altered by medications used in varied clinical settings. Drugs may interfere at different steps in thyroid hormone synthesis or secretion leading to hypothyroidism or thyrotoxicosis or may cause changes in hormone binding leading to difficulties in the interpretation of thyroid function tests. These difficulties have been largely overcome by the development of improved diagnostic tools including radio-active uptake studies, estimation of thyroid auto-antibodies and highly sensitive hormone assays.

Can COX-2 inhibitor-induced increase in cardiovascular disease risk be modified by essential fatty acids?

Selective COX-2 inhibitors increase the risk of myocardial infarction and stroke. This has been attributed to their ability to inhibit endothelial COX-2 derived prostacyclin (PGI2) but not platelet COX-1 derived thromboxane A2 (TXA2). On the other hand, aspirin blocks both COX-1 and COX-2 enzymes without decreasing PGI2 but blocks TXA2 synthesis that explains its beneficial action in the prevention of coronary heart disease (CHD). The inhibitory action of aspirin on COX-1 and COX-2 enzymes enhances the tissue concentrations of dihomo-gamma-linolenic acid (DGLA), arachidonic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). These fatty acids form precursors to PGE1, PGI2, PGI3, lipoxins (LXs), and resolvins that have anti-inflammatory actions. In contrast, increase in the concentrations of DGLA, AA, EPA, and DHA is much less with specific COX-2 inhibitors since they do not block the formation of eicosanoids through COX-1 pathway. COX-2 inhibitors interfere with the formation of LXs and resolvins that have neuroprotective and cardioprotective actions. EPA and PGI2 have anti-arrhythmic action. EPA, DHA, and AA augment eNO formation that prevents atherosclerosis. This suggests that COX-2 inhibitors increase cardiovascular and stroke risk by interfering with the formation of eNO, PGI2, LXs, and resolvins and implies that combining EFAs with COX-2 inhibitors could prevent these complications.

Finasteride-associated male infertility

A finasterida é um potente e específico inibidor da enzima 5a-redutase em homens. Estudos clínicos demonstraram que finasterida 1mg/dia diminui a progressão da queda e aumenta o crescimento do cabelo em homens que sofrem de queda de cabelo hereditária. Por sua influência no metabolismo dos andrógenos existe uma preocupação a respeito do seu uso, principalmente em pacientes em idade fértil. Neste trabalho são descritos 3 casos de pacientes jovens, que apresentaram piora do espermograma durante o uso continuado de finasterida 1mg revertida após a suspensão do mesmo. Dois deles tinham varicocele unilateral e o terceiro era obeso. Aparentemente o tratamento com finasterida promoveu alteração significativa na qualidade seminal. Pode-se especular que talvez a finasterida por si só não traga alteração para a espermatogênese como reportado por Overstreet et al. (1999), mas que em pacientes de risco com possíveis causas de infertilidade associadas, possa ocorrer a amplificação da influência deletéria da finasterida. Estudos futuros devem ser realizados para esclarecer a influência da finasterida nestes pacientes.

An open non-comparative clinical study for the evaluation of safety and efficacy of esomeprazole in patients of reflux oesophagitis in Indian population.

The proton pump inhibitors have consistently been shown to be far more effective than the others are in gastro-oesophageal reflux disease (GERD) as proton pump inhibitors (PPIs) block the final and rate-limiting step of parietal acid production. The primary objective of the study was to assess the efficacy and tolerability of esomeprazole 40 mg given once a day for 4 weeks in patients with reflux oesophagitis. An open, non-comparative study was done with 103 patients in 4 centres with endoscopic erosive oesophagitis. Symptoms of reflux oesophagitis such as heartburn/retrosternal pain and regurgitation recorded on a 4-point scale, dysphagia being marked as present or absent. Oesophagitis was graded as 5-point scale. There was a significant decrease in mean score of heartburn (60.8% and 86%), retrosternal pain (60.84% and 86.75%), mean score of regurgitation (65% and 90%) at second and fourth week respectively. Global assessment of overall symptoms by patients showed complete resolution of symptoms in 86.4% patients at week 4. At the end of treatment 93 out of 103 patients showed complete healing, 13.6% of total cases had side effects. Esomeprazole was found effective and safe in the treatment of GERD.

Ulcera péptica y helicobacter pylori: resultados y consecuencias de su erradicación / Peptic ulcer disease and helicobacter pylori: results and consequences of its eradication

Helicobacter pylori (Hp) causa reconocida de úlcera péptica (UP), provoca más de 90 por ciento de ellas cuando los antiinflamatorios no esteroideos (AINE) son excluidos. La prevalencia de HP en algunas poblaciones subdesarrolladas es superior a 70 por ciento, en tanto que menos de 1 por ciento desarrolla UP. Tal selectividad se ha atribuido a diferencias en patogenicidad de cepas, su proporción relativa en un hu,sped determinado, pero también a factores géneticos del huésped que pedisponen no sólo a su colonización, sino por respuestas inmunológicas diveras produce UP en algunos, en tanto que otros sólo desarrollan gastritis. También otros factores funcionales independientes de Hp como la hipersecreción ácida, o la hiposecreción de bicarbonato duodenal interactúan con Hp para el desarrollo de UP. Los niveles de pepsinógeno I predicen mejor el riesgo de UP que la presencia de Hp. La recurrencia de UP erradicado Hp es de menos del 2 por ciento al año, sin embargo existen controversias en la necesidad de erradicar ante la administración de AINE, toda vez que no previene su aparación, no mejora el tiempo de cicatrización, como tampoco disminuye la frecuencia de hemorragia secundaria. La recurrencia de hemorragia por el contrario es menos frecuente sin Hp. La prevalencia de Hp en hemorragia por UP es asombrosamente semejante a la de la población general de la misma zona geográfica, no parece ser por tanto factor de riesgo para esta complicación. la erradicación de Hp en pacientes con UP provoca esofagitis en 25 por ciento de ellos, como también hace más difícil su control. Peor aún, la hipergastrinemia provocada por antisecretores se acentúa en presencia de Hp son diversas y se necesita de so conocimiento para la adecuada selección de pacientes que requieren erradicación

Effect of inhibition of nitric oxide synthase on blood pressure and renal sodium handling in renal denervated rats

The role of sympathetic nerve activity in the changes in arterial blood pressure and renal function caused by the chronic administration of NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, was examined in sham and bilaterally renal denervated rats. Several studies have demonstrated that sympathetic nerve activity is elevated acutely after L-NAME administration. To evaluate the role of renal nerve activity in L-NAME-induced hypertension, we compared the blood pressure response in four groups (N = 10 each) of male Wistar-Hannover rats weighing 200 to 250 g: 1) sham-operated vehicle-treated, 2) sham-operated L-NAME-treated, 3) denervated vehicle-treated, and 4) denervated L-NAME-treated rats. After renal denervation or sham surgery, one control week was followed by three weeks of oral administration of L-NAME by gavage. Arterial pressure was measured weekly in conscious rats by a tail-cuff method and renal function tests were performed in individual metabolic cages 0, 7, 14 and 21 days after the beginning of L-NAME administration. L-NAME (60 mg kg-1 day-1) progressively increased arterial pressure from 108 + or - 6.0 to 149 + or - 12 mmHg (P<0.05) in the sham-operated group by the third week of treatment which was accompanied by a fall in creatinine clearance from 336 + or - 18 to 222 + or - 59 µl min-1 100 g body weight-1 (P<0.05) and a rise in fractional urinary sodium excretion from 0.2 + or - 0.04 to 1.62 + or - 0.35 per cent (P<0.05) and in sodium post-proximal fractional excretion from 0.54 + or - 0.09 to 4.7 + or - 0.86 per cent (P<0.05). The development of hypertension was significantly delayed and attenuated in denervated L-NAME-treated rats. This was accompanied by a striking additional increase in fractional renal sodium and potassium excretion from 0.2 + or - 0.04 to 4.5 + or - 1.6 per cent and from 0.1 + or - 0.015 to 1.21 + or - 0.37 per cent, respectively, and an enhanced post-proximal sodium excretion compared to the sham-operated group. These differences occurred despite an unchanged creatinine clearance and Na+ filtered load. These results suggest that bilateral renal denervation delayed and attenuated the L-NAME-induced hypertension by promoting an additional decrease in tubule sodium reabsorption in the post-proximal segments of nephrons. Much of the hypertension caused by chronic NO synthesis inhibition is thus dependent on renal nerve activity.

A case of amiodarone and neuromyopathy

La amiodarona es utilizada frecuentemente en el control de las arritmias cardíacas a pesar de sus múltiples efectos colaterales. Se reporta el caso de un varón de 38 años con diagnóstico de taquicardia ventricular que después de un año de uso crónico de amiodarona, presentó fatiga muscular, parestesias y temblor fino fistal en extremidades. Un aumento en la dosis de amiodarona por recidiva de la arritmia fue seguido de una elevación sostenida de los niveles séricos de la fracción MM de creatín fosfocinasa. Una electromiografia reveló neuropatía periférica sensitivo-motora, y una biopsia del cuadriceps, atrofia muscular de tipo neuropático, que se correlacionó con la presencia de depósitos intralisosomales e importante degeneración axonal en el nervio sural. Ambas alteraciones fueron dosis/tiempo dependiente. El caso ilustra la conveniencia de investigar intencionadamente estas alteraciones en pacientes que reciben este fármaco por periodos prolongados