5-Methoxyflavone-induced AMPKα activation inhibits NF-κB and P38 MAPK signaling to attenuate influenza A virus-mediated inflammation and lung injury in vitro and in vivo.

Influenza-related acute lung injury (ALI) is a life-threatening condition that results mostly from uncontrolled replication of influenza virus (IV) and severe proinflammatory responses. The methoxy flavonoid compound 5-methoxyflavone (5-MF) is believed to have superior biological activity in the treatment of cancer. However, the effects and underlying mechanism of 5-MF on IV-mediated ALI are still unclear. Here, we showed that 5-MF significantly improved the survival of mice with lethal IV infection and ameliorated IV-mediated lung edema, lung histological changes, and inflammatory cell lung recruitment. We found that 5-MF has antiviral activity against influenza A virus (IAV), which was probably associated with increased expression of radical S-adenosyl methionine domain containing 2 (RSAD2) and suppression of endosomal acidification. Moreover, IV-infected A549 cells with 5-MF treatment markedly reduced proinflammatory mediator expression (IL-6, CXCL8, TNF-α, CXCL10, CCL2, CCL3, CCL4, GM-CSF, COX-2, and PGE2) and prevented P-IKBα, P-P65, and P-P38 activation. Interestingly, we demonstrated that 5-MF treatment could trigger activation of AMP-activated protein kinase (AMPK)α in IV-infected A549 cells, as evidenced by activation of the AMPKα downstream molecule P53. Importantly, the addition of AMPKα blocker compound C dramatically abolished 5-MF-mediated increased levels of RSAD2, the inhibitory effects on H1N1 virus-elicited endosomal acidification, and the suppression expression of proinflammatory mediators (IL-6, TNF-α, CXCL10, COX-2 and PGE2), as well as the inactivation of P-IKBα, P-P65, and P-P38 MAPK signaling pathways. Furthermore, inhibition of AMPKα abrogated the protective effects of 5-MF on H1N1 virus-mediated lung injury and excessive inflammation in vivo. Taken together, these results indicate that 5-MF alleviated IV-mediated ALI and suppressed excessive inflammatory responses through activation of AMPKα signaling.

In vitro and in vivo neuroprotective effect of novel mPGES-1 inhibitor in animal model of Parkinson's disease.

mPGES-1 is found to be up-regulated in the dopaminergic neurons of the substantia nigra pars compacta (SNpc) of postmortem brain tissue from Parkinson's disease (PD) patients and neurotoxin 6-hydroxydopamine (6-OHDA)-induced PD mice. Since the genetic deletion of mPGES-1 abolished 6-OHDA-induced PGE2 production and 6-OHDA-induced dopaminergic neurodegeneration in vitro and in vivo models, mPGES-1 enzyme has the potential to be an important target for PD therapy. In the present work, we investigated whether a small organic molecule as mPGES-1 inhibitor could exhibit the neuroprotective effects against 6-OHDA-induced neurotoxicity in in vitro and in vivo models. For this research goal, a new series of arylsulfonyl hydrazide derivatives was prepared and investigated whether these compounds may protect neurons against 6-OHDA-induced neurotoxicity in both in vitro and in vivo studies. Among them, compound 7s (MPO-0144) as a mPGES-1 inhibitor (PGE2 IC50 = 41.77 nM; mPGES-1 IC50 = 1.16 nM) exhibited a potent neuroprotection (ED50 = 3.0 nM) against 6-OHDA-induced in PC12 cells without its own neurotoxicity (IC50 = >10 µM). In a 6-OHDA-induced mouse model of PD, administration of compound 7s (1 mg/kg/day, for 7 days, i.p.) ameliorated motor impairments and dopaminergic neuronal damage. These significant biological effects of compound 7s provided the first pharmacological evidence that mPGES-1 inhibitor could be a promising therapeutic agent for PD patients.

TamaFlex™-A novel nutraceutical blend improves lameness and joint functions in working horses.

BACKGROUND: Lameness is one of the major causes of reduced physical performance and early retirement in working horses. TamaFlex™ (NXT15906F6) is a standardized synergistic anti-inflammatory botanical formulation containing Tamarindus indica seed extract and Curcuma longa rhizome extract at a 2:1 ratio. METHODS: We conducted a 12-week single-center, randomized, blinded, placebo-controlled trial demonstrating the efficacy of NXT15906F6 in horses with lameness grade 2-4 on the American Association of Equine Practitioners (AAEP) scale. Twenty-two lame horses were supplemented with NXT15906F6 (2.5 gram/day) or placebo over a period of 84 days. Improvement in lameness over placebo was the primary endpoint, and changes in the levels of rheumatoid factor (RF), anti-nuclear antibody (ANA), and anti-cyclic citrullinated peptide (ACC-peptide) in serum, and pro-inflammatory cytokines including interleukin (IL-1ß and IL-6), tumor necrosis factor-α (TNF-α) and prostaglandin-E2 (PGE2 ) in serum and synovial fluid were the secondary endpoints. RESULTS: NXT15906F6 exhibited significant relief from lameness in a time-dependent manner. NXT15906F6 also reduced levels of ANA, PGE2 , IL-1ß, TNF-α and IL-6. Moreover, NXT15906F6 supplementation is safe and tolerable in alleviating joint pain in lame horses, and protects the joints from further degradation by reducing pro-inflammatory mediators. CONCLUSION: NXT15906F6 significantly reduces the lameness during walking and trotting, leading to an improvement in their joint flexibility, health, and working performances.

Role of ADMA/DDAH-1 and iNOS/eNOS signaling in the gastroprotective effect of tadalafil against indomethacin-induced gastric injury.

Non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastric ulcers represent a significant clinical concern and adversely affect the quality of life. Inducible nitric oxide synthase/endothelial nitric oxide synthase (iNOS/eNOS) and asymmetric dimethylarginine/ dimethylarginine dimethylaminohydrolase-1 (ADMA/DDAH-1) signaling are key players in gastric ulcer pathogenesis. This work was planned to explore the role of iNOS/eNOS and ADMA/DDAH-1 signaling in rats with indomethacin-induced gastric ulcer, as potential pathways for the gastro-protective effect of tadalafil. Split into 5 separate groups, rats were assigned to control, tadalafil (10 mg/kg, p.o), indomethacin (single oral dose of 60 mg/kg), indomethacin + pantoprazole (40 mg/kg, p.o), and indomethacin + tadalafil (10 mg/kg, p.o). The results indicated that pretreatment with tadalafil significantly reduced ulcer index (UI), increased preventive index (PI), and counteracted indomethacin-induced histopathological aberrations. Tadalafil significantly reduced the gastric content of NO while it significantly elevated that of GSH and enhanced SOD activity. It significantly reduced the gastric expression of TNF-α and ADMA while it significantly elevated that of COX-2, PGE-2, and DDAH-1. Western blot analysis revealed that pretreatment with tadalafil significantly reduced iNOS protein expression while it significantly elevated that of eNOS. Collectively, these data suggest that tadalafil exerts potential protective effect against indomethacin-induced ulcer through suppression of inflammation, attenuation of oxidative stress, and boosting of antioxidants. Moreover, tadalafil protective effects are mediated via upregulation of PGE-2 with modulating the signaling pathways of ADMA/DDAH-1, and iNOS/eNOS. As a result, the current evidence corroborates the use of tadalafil in controlling gastric ulcers and preventing NSAID gastric side effects.

Salicylic acid-based hypoxia-responsive chemodynamic nanomedicines boost antitumor immunotherapy by modulating immunosuppressive tumor microenvironment.

The delivery of salicylic acid or its derivatives to tumor tissue in the form of nanomedicine is critical for the studies on their potential synergistic mechanism in tumor therapy and chemoprevention considering the dangerous bleeding in the high-dose oral administration. To deepen the understanding of their role in adjusting immunosuppressive tumor microenvironment (ITM), herein, we firstly developed a hypoxia-sensitive Fe-5,5'-azosalicylic acid nanoscale coordination polymer nanomedicines (FeNCPs) via a "old drugs new tricks" strategy for synergistic chemodynamic therapy (CDT) and remodulation of ITM to elevate antitumor immunotherapy effect. PEGylated FeNCPs could be reductively cleaved to release 5-aminosalicylic acid (5-ASA) and ferric ions by azo-reductase under hypoxic conditions, which could induce tumor cell death by Fenton reaction-catalysis enhanced CDT and 5-ASA-converted carboxylquinone to promote the production of •OH. Meanwhile, cyclooxygenase-2 (COX-2) and its enzymatic product prostaglandin E2 (PGE2), as immune negative regulatory molecules, can promote tumor progression and immune tolerance. The released 5-ASA as a COX inhibitor could suppress the expression of PGE2, and Fe3+ was employed to reeducate M2-like tumor-associated macrophages (TAMs) to M1-like phenotype, which could initiate antitumor immune response to reach better antitumor immunotherapy. This work broadens the application of salicylic acid derivatives in antitumor immunotherapy, and provides a new strategy for their "old drugs new tricks". STATEMENT OF SIGNIFICANCE: Cyclooxygenase-2 (COX-2) and its enzymatic product prostaglandin E2 (PGE2), as immune negative regulatory molecules, facilitate the differentiation of immune cells into immunosuppressive cells to build the immunosuppressive tumor microenvironment, which can promote tumor progression and immune tolerance. Thus, down-regulation of COX-2/PGE2 expression may be a key approach to tumor treatments. Meanwhile, as a class of inhibitors of COX-2/PGE2, the potential mechanism of aspirin or 5-aminosalicylic acid has been a mystery in tumor therapy and chemoprevention. To expand the application of aspirin family nanomedicine in biomedicine, herein, we firstly developed a hypoxia-sensitive Fe-5,5'-azosalicylic acid nanoscale coordination polymer nanomedicines via a "old drugs new tricks" strategy for synergistic chemodynamic therapy and remodulation of immunosuppressive tumor microenvironment to elevate antitumor immunotherapy effect.

Plasma renin, aldosterone, and urinary prostaglandin E2 levels in children with hypocalcemia due to vitamin D deficiency rickets.

We investigated the effect of hypocalcemia on plasma renin, aldosterone, and urine PGE2 levels in children with vitamin D deficiency rickets (VDDR). In the study group, 25 patients with VDDR-induced hypocalcemia were treated with a single dose of 150,000-300,000 IU cholecalciferol and 50 mg/kg/day elemental Ca for 10 days. On any day between 21th and 30th days after the treatment, the patients' clinical, biochemical and radiologic findings were re-evaluated. The healthy children with the same sex and similar age as the study group comprised the control group. Plasma sodium (Na), potassium (K), calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), parathyroid hormone (PTH), 25- hydroxy vitamin D (25OHD), renin, aldosterone; and urinary Ca, creatinine (Cr) and prostaglandin E2 (PGE2) levels were measured in both the study (pre-treatment and post-treatment) and the control group. Plasma Ca, P, 25OHD and renin levels and urinary PGE2/Cr ratio in the post-treatment group were significantly higher than those in the pre-treatment group while K, ALP, and PTH concentrations were significantly lower. Plasma ALP and PTH levels in pre-treatment group were significantly higher than in the control group while Ca, P, 25OHD, aldosterone and renin concentrations and urinary PGE2/Cr ratio were significantly lower. Post-treatment plasma Ca level was significantly decreased in normal limits compared to the control group while other biochemical parameters were not different from the control group. Plasma Ca concentration was positively correlated with renin level and urinary PGE2/Cr ratio. The findings suggest that hypocalcemia may inhibit the production of renin, aldosterone and PGE2 and a blunt aldosterone secretion may develop even after recovery from hypocalcemia.

Citric Acid-Enriched Extract of Ripe Prunus mume (Siebold) Siebold & Zucc. Induces Laxative Effects by Regulating the Expression of Aquaporin 3 and Prostaglandin E2 in Rats with Loperamide-Induced Constipation.

Previously, we demonstrated that extracts of the ripe fruit (rPM) and unripe fruit (uPM) of Prunus mume (Siebold) Siebold & Zucc. and citric acid have a laxative effect, which is at least partially mediated by the increase in fecal parameters as seen in the low-fiber diet-induced constipation model rats. This study aims at investigating the laxative effects of citric acid-enriched aqueous extracts of rPM, uPM, and its active compounds, such as citric acid and malic acid, on loperamide-induced constipation rat models. Animal studies were conducted with loperamide-induced constipation animal models. The results showed that rPM and citric acid, the major organic acid compounds, significantly improved stool parameters (number, weight, and water content of the stools) generated in loperamide-induced constipation rats, without adverse effects of diarrhea. The gastrointestinal (GI) motility was activated fully in the rPM- and citric acid-treated rats than in rats treaded with loperamide alone. In addition, when rPM and citric acid were added to RAW264.7 cells and used to treat loperamide-induced constipation model rats, the secretion of prostaglandin E2 (PGE2) increased significantly in cells and tissue. Furthermore, rPM and citric acid decreased the expression of the aquaporin 3 (AQP3) in the rat colons. Our results demonstrated that rPM and citric acid, the major organic acid compound in rPM, can effectively promote defecation frequency and regulate PGE2 secretion and AQP3 expression in the colon, providing scientific evidence to support the use of rPM as a therapeutic application.

Importancia de la rehabilitación precoz de los cuerpos cavernosos tras prostatectomía radical / Importance of early rehabilitation of the corpus cavernosum after radical prostatectomy

Objetivos: Primario: evaluar la importancia de una rehabilitación precoz de los cuerpos cavernosos sobre la función eréctil tras prostatectomía radical. Secundario: analizar los factores asociados a una mejor respuesta. Material y método: Estudio retrospectivo en pacientes tratados con inyecciones intracavernosas tras prostatectomía radical entre el 1 de enero de 2006 y el 31 de diciembre de 2008. Se incluyeron enfermos sin antecedentes de disfunción eréctil previa a la cirugía, no respondedores a inhibidores de la 5-fosfodiesterasa. En todos se realizó ecodoppler color tras inyección de prostaglandina E1 10-20 mg. Se compararon 2 grupos en función de la precocidad del inicio de la rehabilitación tras la cirugía (precoz, < 6 meses, o tardía, > 6 meses). Resultados: Se incluyeron 82 pacientes. En el análisis multivariante, fueron factores predictores de buena respuesta al tratamiento: inicio precoz de la rehabilitación (OR: 0,06; IC 95%: 0,014- 0,26), mayor velocidad pico sistólica durante el test (OR: 1,01; IC 95%: 1,01-1,1) y estadio anatomopatológico favorable (OR: 0,15; IC 95%: 0,036-0,6). El ecodoppler color tras inyección de prostaglandina E1 presentó valores anormales con mayor frecuencia en el grupo de inicio tardío frente al precoz (89,5% [n = 34] vs. 65,9% [n = 29]; p = 0,01). El 40,2% (n = 33) de los sujetos presentaron fracaso del mecanismo corporovenooclusivo, presentando valores más elevados el grupo de inicio tardío (5,53 ± 1,4 cm/seg) frente al precoz (4,75 ±1,03 cm/seg) (p = 0,005). La presencia de erecciones funcionales a los 18 meses del seguimiento fue mayor en el grupo de inicio precoz (p < 0,001). Conclusiones: Según el presente estudio, en pacientes tras prostatectomía radical la rehabilitación farmacológica precoz de la erección presenta mejores resultados comparada con la tardía (AU)

Objectives: Primary: to evaluate the importance of early rehabilitation of the corpus cavernosum on erectile function after radical prostatectomy. Secondary: to analyse the factors associated with better response. Material and method: Retrospective study in patients treated with intracavernous injections after radical prostatectomy between 1 January 2006 and 31 December 2008. We included patients lacking a history of erectile dysfunction prior to surgery, not responding to phosphodiesterase-5 inhibitors. All patients underwent colour echo-doppler after injection of prostaglandin E1 10-20 mg. The outcomes of these 2 groups were then compared according to how early rehabilitation began after surgery (early, < 6 months, or late, > 6 months). Results: There were 82 patients included in the study. In the multivariate analysis, predictive factors of good response to treatment were: early onset of rehabilitation (OR: 0.06; 95% CI: 0.014-0.26), higher peak systolic velocity during the test (OR: 1.01; 95% CI: 1.01-1.1) and favourable histopathological stage (OR: 0.15; 95% CI 95%: 0.036-0.6). The colour echo-doppler procedure after prostaglandin E1 injection showed abnormal values more frequently in the lateonset than in the early group (89.5% [n = 34] vs. 65.9% [n = 29]; P = .01). Corporal veno-occlusive dysfunction was presented by 40.2% (n = 33) of subjects, with the late-onset group presenting higher values (5.53 ± 1.4 cm/sec) than the early group (4.75 ± 1.03 cm/sec) (P = .005). The presence of functional erections at 18 months’ follow-up was higher in the early onset group (P < .001). Conclusions: According to this study, early erectile dysfunction rehabilitation after radical prostatectomy achieves better results than late rehabilitation in patients (AU)

Regulación de la neurotransmisión glicinérgica en procesos de dolor inflamatorio: una nueva vía de acción de la prostaglandina E2 en médula espinal / Regulation of the glycinergic neurotransmission during inflammatory pain: A new pathway in the action of Prostaglandin E2 in the spinal cord

La acción de la glicina como neurotransmisor inhibidor es finalizada por su recaptación del espacio sináptico a través de dos transportadores específicos, GlyT1 (isoforma glial) y GlyT2 (isoforma neuronal). En este trabajo describimos un mecanismo mediante el cual la unión de la prostaglandina E2 (un importante mediador del dolor inflamatorio) a sus receptores EP3 activa la recaptación de glicina llevada a cabo por GlyT2. Esta activación coincide con una disminución de la ubiquitinación del transportador, modificación post-traduccional necesaria para su correcto tráfico intracelular. Una menor ubiquitinación de GlyT2 produce una acumulación del transportador en la superficie neuronal, lo que explica la activación observada. Por tanto, los resultados de este trabajo sugieren que GlyT2 es una interesante diana terapéutica cuya inhibición podría contribuir a la reducción del dolor inflamatorio (AU)

Glycinergic inhibitory neurotransmission is terminated by reuptake through specific transporters, GlyT1 (glial isoform) and GlyT2 (neuronal isoform). In this work we describe that Prostaglandin E2 (PGE2, an important mediator of inflammatory pain) activates GlyT2-mediated recapture of glycine via interaction with the EP3 receptor. Moreover, in these conditions a diminished ubiquitination of GlyT2 is observed. Ubiquitination is an important modification for the correct trafficking of this transporter. We propose that the reduction of ubiquitination leads to accumulate GlyT2 in the neuronal surface, which could explain the PGE2-mediated activation of GlyT2. Therefore, our results suggest that GlyT2 is an interesting therapeutic target and its inhibition could contribute to reduce inflammatory pain (AU)

Hiperostosis cortical neonatal: un efecto colateral de la administración prolongada de prostaglandinas E1 / Neonatal cortical hyperostosis: a side effect of prolonged prostaglandin E1 infusion

La infusión de prostaglandinas E1 (PGE1) es habitualmente administradapor tiempos cortos para mantener la permeabilidad del ductus arterioso en lactantes con cardiopatías congénitas. En pacientes a la espera de la cirugía cardíaca el tratamiento puede prolongarse. Pueden ocurrir efectos colaterales, en su mayoría reversibles con la supresión del tratamiento. La hiperostosis cortical es una complicación frecuente de la administración prolongada de PGE1.Objetivo: Determinar la incidencia y gravedad de la hiperostosis cortical en neonatos que requieren infusión prolongada de prostaglandinas E1. Se estudiaron 61 recién nacidos con cardiopatías congénitas admitidos en la Unidad de Cuidados Intensivos Neonatales de la Clínica Bazterrica, desde enero del 2006 hasta mayo del 2010. Cinco recién nacidos recibieron tratamiento prolongado con PGE1. Cuatro presentaron evidenciaclínica y radiológica de hiperostosis cortical con elevados niveles séricos de fosfatasa alcalina. Diagnosticar esta entidad permitirá evitar estudios complementarios innecesarios o la suspensión de la cirugía cardíaca.

Prostaglandin E1 (PGE1) infusion is usually administered for short periods to maintain patency of ductus arteriosus in infants with cyanotic heart disease. Prolonged therapy may be necessary while patients are awaiting surgical treatment. Several side effects occur at the onset of the treatment, most of them reversible once the treatment is discontinued. Cortical hyperostosis is a frequent complication of prolonged PGE1 infusion. Objective is to determine the incidence and severity of cortical hyperostosis in newborn requiring prolonged prostaglandin E1 infusion. 61 newborn babies were admitted in the Neonatal Intensive Care Unit at Bazterrica Clinic, Buenos Aires City, from January 2006 to May 2010. Five newborn received prolonged PGE1 therapy defined as a longer-than-one-week treatment. Four of them had radiologic evidence of cortical hyperostosis and elevated serum alkaline phosphatase. Accurate and rapid diagnosis of this condition is critical to reduce unnecessary laboratory tests and to avoid cardiac surgery canceling.

Hiperostosis cortical neonatal: un efecto colateral de la administración prolongada de prostaglandinas E1 / Neonatal cortical hyperostosis: a side effect of prolonged prostaglandin E1 infusion

La infusión de prostaglandinas E1 (PGE1) es habitualmente administradapor tiempos cortos para mantener la permeabilidad del ductus arterioso en lactantes con cardiopatías congénitas. En pacientes a la espera de la cirugía cardíaca el tratamiento puede prolongarse. Pueden ocurrir efectos colaterales, en su mayoría reversibles con la supresión del tratamiento. La hiperostosis cortical es una complicación frecuente de la administración prolongada de PGE1.Objetivo: Determinar la incidencia y gravedad de la hiperostosis cortical en neonatos que requieren infusión prolongada de prostaglandinas E1. Se estudiaron 61 recién nacidos con cardiopatías congénitas admitidos en la Unidad de Cuidados Intensivos Neonatales de la Clínica Bazterrica, desde enero del 2006 hasta mayo del 2010. Cinco recién nacidos recibieron tratamiento prolongado con PGE1. Cuatro presentaron evidenciaclínica y radiológica de hiperostosis cortical con elevados niveles séricos de fosfatasa alcalina. Diagnosticar esta entidad permitirá evitar estudios complementarios innecesarios o la suspensión de la cirugía cardíaca.(AU)

Prostaglandin E1 (PGE1) infusion is usually administered for short periods to maintain patency of ductus arteriosus in infants with cyanotic heart disease. Prolonged therapy may be necessary while patients are awaiting surgical treatment. Several side effects occur at the onset of the treatment, most of them reversible once the treatment is discontinued. Cortical hyperostosis is a frequent complication of prolonged PGE1 infusion. Objective is to determine the incidence and severity of cortical hyperostosis in newborn requiring prolonged prostaglandin E1 infusion. 61 newborn babies were admitted in the Neonatal Intensive Care Unit at Bazterrica Clinic, Buenos Aires City, from January 2006 to May 2010. Five newborn received prolonged PGE1 therapy defined as a longer-than-one-week treatment. Four of them had radiologic evidence of cortical hyperostosis and elevated serum alkaline phosphatase. Accurate and rapid diagnosis of this condition is critical to reduce unnecessary laboratory tests and to avoid cardiac surgery canceling.(AU)

A novel hybrid therapy for pulmonary atresia with intact ventricular septum.

There exists some controversy over how to treat patients of pulmonary atresia with intact ventricular septum: transcatheter or open chest. Each has certain drawbacks. We describe a novel hybrid approach which has the advantages of both methods.

Interventions for the prevention and treatment of herpes simplex virus in patients being treated for cancer.

BACKGROUND: Treatment of cancer is increasingly effective, but associated with oral complications such as mucositis, fungal infections, bacterial infections and viral infections such as the herpes simplex virus (HSV). OBJECTIVES: To examine the effects of interventions for the prevention or treatment or both, of herpes simplex virus in patients receiving treatment for cancer. SEARCH STRATEGY: We searched the following databases: Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE, EMBASE, CINAHL, CANCERLIT, SIGLE and LILACS. The reference list of all related review articles and articles considered to be potentially relevant were checked for further trials. Authors of identified trials and known specialists in the field were also contacted in an attempt to identify any additional published or unpublished trials. Date of most recent search: November 2008. SELECTION CRITERIA: All randomised controlled trials comparing interventions for the prevention or treatment or both of HSV infection in people being treated for cancer. Outcomes were presence/absence of clinical/culture positive HSV infections (prevention), time to complete healing of lesions (treatment), duration of viral shedding, recurrence of lesions, relief of pain, amount of analgesia, duration of hospital stay, cost of oral care, patient quality of life and adverse effects. DATA COLLECTION AND ANALYSIS: Data were independently extracted, in duplicate, by two review authors. Authors were contacted for details of randomisation, blindness and sample demographics where necessary. Quality assessment was carried out on randomisation, blindness, withdrawals and selective reporting. The Cochrane Collaboration's statistical guidelines were followed and risk ratio (RR) values were calculated using random-effects models. MAIN RESULTS: Seventeen trials satisfied the inclusion criteria. Four trials evaluated preventative interventions for HSV lesions, three trials for viral isolates, and eight trials evaluated both outcome measures. A single trial reported on the cost of prophylaxis for HSV. Two trials evaluating treatment reported on time to healing, duration of viral shedding and relief of pain. No trials reported on duration of hospital stay, amount of analgesia or patient quality of life.In placebo controlled trials, aciclovir was found to be effective for the prevention of HSV infections as measured by oral lesions or viral isolates (RR = 0.16, 95% confidence interval (CI) 0.08 to 0.31 nine trials; RR = 0.17, 95% CI 0.07 to 0.37 nine trials). There is no evidence that valaciclovir is more efficacious than aciclovir, or that higher doses of valaciclovir are more effective than lower doses. Placebo was found to be more effective than prostaglandin E for prevention of viral isolates (RR = 1.87, 95% CI 1.12 to 3.14 one trial).Aciclovir was also found to be effective for the treatment of HSV in terms of duration of viral shedding (median of 2.5 days versus 17.0 days, P = 0.0002; 2 days compared to more than 9, P = 0.0008), time to first decrease in pain (median 3 days compared to 16, P = 0.04), complete resolution of pain (9.9 days compared to 13.6 days, P = 0.01; median of 6 days compared to 16, P = 0.05), 50% healing (median of 6 days compared to 11, P = 0.01) and total healing (median 13.9 days compared to 20.7 days, P = 0.08; median of 8 days compared to 21, P = 0.0). AUTHORS' CONCLUSIONS: There is evidence that aciclovir is efficacious in the prevention and treatment of herpes simplex virus infections. There is no evidence that valaciclovir is more efficacious than aciclovir, or that a high dose of valaciclovir is better than a low dose of valaciclovir. There is evidence that as a prophylaxis, placebo is more efficacious than prostaglandin E. However, in all included trials, risk of bias is unclear.

Lactante con acrocianosis simétrica de ambos pies / Infant with symmetric acrocyanosis of both feet

No disponible

Tratamiento con PGE1 (Alprostadil alfadex) del embolismo por cristales de colesterol / Cholesterol crystals atheroembolic: treatment with PGE1 (Alprostadil alfadex)

Presentamos un caso de enfermedad ateroembólica por cristales de colesterol que fue tratado con prostaglandinas durante 90 días consiguiendo un resultado favorable. Indicamos el planteamiento diagnóstico y terapéutico en esta difícil patología

This paper reports on a case of cholesterol crystal embolization treated with prostaglandins over a 90-day period with a favourable outcome. The diagnostic and therapeutic approach to this complex pathology is discussed

Role of ATP-sensitive K+ channels in relaxation of penile resistance arteries.

OBJECTIVES: To investigate the functional presence of adenosine triphosphate (ATP)-sensitive potassium (K+) channels (K(ATP)) in penile resistance arteries by evaluating the relaxant effects of the selective K(ATP) channel openers, cromakalim and levcromakalim, and also the involvement of K(ATP) channels in the relaxation of two drugs currently used in the treatment of erectile dysfunction (ie, prostaglandin E1 [PGE1] and sildenafil). METHODS: Penile resistance arteries were dissected from the horse corpus cavernosum and mounted in microvascular myographs for isometric tension recording. The arteries were precontracted with phenylephrine, and the responses to several vasodilators were tested in the absence and presence of K+ channel blockers. RESULTS: Cromakalim and levcromakalim evoked complete concentration-dependent relaxations that were blocked by 3 microm of the selective K(ATP) channel inhibitor glibenclamide. Raising extracellular K+ (25 mM) inhibited the relaxations to PGE1 and to the selective inhibitor of the cyclic adenosine monophosphate-specific phosphodiesterase (PDE4) rolipram. At a concentration selective for calcium-activated K+(K(Ca)) channels (3 mM), tetraethylammonium inhibited rolipram responses but not those of PGE1. However, glibenclamide significantly reduced the relaxation to both PGE1 and rolipram, but not those induced by the selective inhibitor of the type 5 cyclic guanosine monophosphate-specific phosphodiesterase (PDE5). CONCLUSIONS: The present results suggest a functional role for K(ATP) channels in the relaxation of penile resistance arteries, as well as their differential involvement in the vasodilation to drugs used in the treatment of organic erectile dysfunction. They mediated relaxation to PGE1 and cyclic adenosine monophosphate-elevating agents, but not those of cyclic guanosine monophosphate-elevating agents such as sildenafil.