RESUMEN
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.
Asunto(s)
Lesión Pulmonar Aguda , Subtipo H1N1 del Virus de la Influenza A , Virus de la Influenza A , Proteínas Quinasas Activadas por AMP/metabolismo , Lesión Pulmonar Aguda/metabolismo , Animales , Antivirales/farmacología , Ciclooxigenasa 2 , Flavonas , Flavonoides/farmacología , Flavonoides/uso terapéutico , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/uso terapéutico , Inflamación/tratamiento farmacológico , Subtipo H1N1 del Virus de la Influenza A/metabolismo , Virus de la Influenza A/metabolismo , Interleucina-6/metabolismo , Metionina/farmacología , Metionina/uso terapéutico , Ratones , FN-kappa B/metabolismo , Prostaglandinas E/farmacología , Prostaglandinas E/uso terapéutico , Factor de Necrosis Tumoral alfa/metabolismo , Proteína p53 Supresora de Tumor , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
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.
Asunto(s)
Fármacos Neuroprotectores , Enfermedad de Parkinson , Animales , Modelos Animales de Enfermedad , Neuronas Dopaminérgicas , Ratones , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Oxidopamina/farmacología , Enfermedad de Parkinson/tratamiento farmacológico , Prostaglandinas E/farmacología , Prostaglandinas E/uso terapéutico , RatasRESUMEN
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.
Asunto(s)
Enfermedades de los Caballos , Cojera Animal , Animales , Antiinflamatorios , Citocinas/uso terapéutico , Suplementos Dietéticos , Enfermedades de los Caballos/tratamiento farmacológico , Enfermedades de los Caballos/metabolismo , Caballos , Mediadores de Inflamación/uso terapéutico , Interleucina-6 , Cojera Animal/tratamiento farmacológico , Cojera Animal/prevención & control , Extractos Vegetales/uso terapéutico , Prostaglandinas/uso terapéutico , Prostaglandinas E/uso terapéutico , Factor Reumatoide , Factor de Necrosis Tumoral alfaRESUMEN
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.
Asunto(s)
Hipocalcemia , Raquitismo , Deficiencia de Vitamina D , Aldosterona/uso terapéutico , Fosfatasa Alcalina/uso terapéutico , Calcio/uso terapéutico , Calcio/orina , Niño , Colecalciferol/uso terapéutico , Creatinina/uso terapéutico , Dinoprostona/uso terapéutico , Humanos , Hipocalcemia/tratamiento farmacológico , Hormona Paratiroidea/uso terapéutico , Fósforo/uso terapéutico , Potasio/uso terapéutico , Prostaglandinas E/uso terapéutico , Prostaglandinas E/orina , Renina/uso terapéutico , Raquitismo/tratamiento farmacológico , Sodio , Vitamina D/uso terapéutico , Deficiencia de Vitamina D/tratamiento farmacológicoRESUMEN
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 â¢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.
Asunto(s)
Neoplasias , Microambiente Tumoral , Aspirina/farmacología , Línea Celular Tumoral , Ciclooxigenasa 2 , Humanos , Hipoxia , Factores Inmunológicos/farmacología , Inmunoterapia , Mesalamina/farmacología , Mesalamina/uso terapéutico , Nanomedicina , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Polímeros/farmacología , Prostaglandinas E/farmacología , Prostaglandinas E/uso terapéutico , Ácido Salicílico/farmacología , Ácido Salicílico/uso terapéuticoRESUMEN
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.
Asunto(s)
Indometacina , Úlcera Gástrica , Amidohidrolasas/metabolismo , Animales , Antiinflamatorios no Esteroideos/uso terapéutico , Arginina/farmacología , Indometacina/uso terapéutico , Indometacina/toxicidad , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Prostaglandinas E/uso terapéutico , Calidad de Vida , Ratas , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/prevención & control , Tadalafilo/farmacología , Tadalafilo/uso terapéutico , Úlcera/tratamiento farmacológicoRESUMEN
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.
Asunto(s)
Laxativos , Prunus , Animales , Acuaporina 3 , Ácido Cítrico/uso terapéutico , Estreñimiento/inducido químicamente , Estreñimiento/tratamiento farmacológico , Loperamida , Prostaglandinas/uso terapéutico , Prostaglandinas E/uso terapéutico , RatasRESUMEN
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.
Asunto(s)
Humanos , Masculino , Femenino , Recién Nacido , Cardiopatías Congénitas , Hiperostosis , Osteocondrodisplasias , Prostaglandinas E/uso terapéutico , Prostaglandinas/efectos adversosRESUMEN
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.
Asunto(s)
Cateterismo , Atresia Pulmonar/terapia , Tabique Interventricular , Cianosis/etiología , Cianosis/terapia , Femenino , Humanos , Recién Nacido , Prostaglandinas E/uso terapéutico , Atresia Pulmonar/complicaciones , Atresia Pulmonar/diagnóstico por imagen , Atresia Pulmonar/fisiopatología , Resultado del Tratamiento , Ultrasonografía , Tabique Interventricular/diagnóstico por imagenRESUMEN
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.
Asunto(s)
Antivirales/uso terapéutico , Herpes Labial/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Estomatitis Herpética/tratamiento farmacológico , Aciclovir/análogos & derivados , Aciclovir/uso terapéutico , Herpes Labial/prevención & control , Humanos , Huésped Inmunocomprometido , Prostaglandinas E/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Simplexvirus , Estomatitis Herpética/prevención & control , Valaciclovir , Valina/análogos & derivados , Valina/uso terapéuticoRESUMEN
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.
Asunto(s)
Adenosina Trifosfato/antagonistas & inhibidores , Cromakalim/farmacología , Pene/irrigación sanguínea , Bloqueadores de los Canales de Potasio/farmacología , Canales de Potasio/efectos de los fármacos , Vasodilatadores/farmacología , Adenosina Trifosfato/fisiología , Animales , Arterias/efectos de los fármacos , Arterias/fisiología , Disfunción Eréctil/tratamiento farmacológico , Disfunción Eréctil/fisiopatología , Gliburida/farmacología , Caballos , Humanos , Masculino , Relajación Muscular/efectos de los fármacos , Relajación Muscular/fisiología , Músculo Liso Vascular/irrigación sanguínea , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/fisiología , Pene/efectos de los fármacos , Piperazinas/farmacología , Piperazinas/uso terapéutico , Canales de Potasio/fisiología , Prostaglandinas E/farmacología , Prostaglandinas E/uso terapéutico , Purinas , Citrato de Sildenafil , Sulfonas , Resistencia Vascular/efectos de los fármacos , Resistencia Vascular/fisiología , Vasodilatación/efectos de los fármacos , Vasodilatación/fisiologíaAsunto(s)
Tromboangitis Obliterante , Adulto , Analgésicos Opioides/uso terapéutico , Angiografía de Substracción Digital , Antihipertensivos/uso terapéutico , Aspirina/administración & dosificación , Aspirina/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico , Diagnóstico Diferencial , Estudios de Seguimiento , Humanos , Masculino , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/uso terapéutico , Pronóstico , Prostaglandinas E/uso terapéutico , Cese del Hábito de Fumar , Tromboangitis Obliterante/diagnóstico , Tromboangitis Obliterante/diagnóstico por imagen , Tromboangitis Obliterante/tratamiento farmacológico , Factores de Tiempo , Tramadol/uso terapéutico , Resultado del Tratamiento , Ultrasonografía Doppler en Color , Vasodilatadores/uso terapéuticoAsunto(s)
Anomalía de Ebstein/diagnóstico , Anomalía de Ebstein/terapia , Tamizaje Neonatal , Óxido Nítrico/uso terapéutico , Administración por Inhalación , Biomarcadores/sangre , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Procedimientos Quirúrgicos Cardíacos , Anomalía de Ebstein/mortalidad , Ecocardiografía , Estudios de Seguimiento , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Humanos , Concentración de Iones de Hidrógeno , Bienestar del Lactante , Recién Nacido , Dióxido de Nitrógeno/sangre , Oxígeno/sangre , Prostaglandinas E/uso terapéutico , Atresia Pulmonar/diagnóstico , Atresia Pulmonar/mortalidad , Atresia Pulmonar/terapia , Circulación Pulmonar/fisiología , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Resultado del TratamientoAsunto(s)
Citocinas/efectos de los fármacos , Lupus Eritematoso Sistémico/etiología , Prostaglandinas E/uso terapéutico , Enfermedad de Raynaud/tratamiento farmacológico , Adulto , Animales , Femenino , Citometría de Flujo , Humanos , Ratones , Enfermedad de Raynaud/complicaciones , Recurrencia , Linfocitos T/efectos de los fármacosAsunto(s)
Trabajo de Parto Inducido , Óxido Nítrico/sangre , Prostaglandinas E/uso terapéutico , Adulto , Femenino , Edad Gestacional , Humanos , Recién Nacido , Inicio del Trabajo de Parto/sangre , Inicio del Trabajo de Parto/efectos de los fármacos , Masculino , Edad Materna , Paridad , Embarazo , Resultado del EmbarazoRESUMEN
OBJECTIVE: To evaluate the incidence of pharmacologically induced priapism in the diagnostic and therapeutic management of erectile dysfunction. PATIENTS AND METHODS: Over a period of 7 years, 685 men were investigated for erectile failure. They underwent a simple test with vaso-active drugs, and the nonresponders were further investigated. Eventually, 83 men began autoinjections and 45 still continue. RESULTS: Eight (1.2%) cases of priapism presented during the simple test with vaso-active drugs in these patients, while none occurred during self-injection treatment. Three were prolonged erections induced by prostaglandin E1 (PGE1) and 5 by papaverine (Pap). Six were treated safely with intracavernosal injection of etilephrine without blood aspiration. CONCLUSION: Priapism is always a potential phenomenon where no individual, no particular drug and no specific dose are completely safe. It may be caused even with 5 microg of PGE1 or 7.5 mg of Pap. Auto-injection therapy however is a safe kind of treatment in well-experienced patients. Careful regulation of the doses and practice in the use of vaso-active drugs may reduce the priapism rate.
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Disfunción Eréctil/diagnóstico , Disfunción Eréctil/tratamiento farmacológico , Papaverina/efectos adversos , Priapismo/inducido químicamente , Priapismo/epidemiología , Prostaglandinas E/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Papaverina/uso terapéutico , Pronóstico , Prostaglandinas E/uso terapéutico , Medición de Riesgo , Factores de RiesgoRESUMEN
OBJECTIVE: Necrotizing enterocolitis (NEC) is primarily a disease of the premature infant. Among children born at term, however, congenital heart disease may be an important predisposing factor for this condition. To determine risk factors for NEC in patients with congenital heart disease, we conducted a case-control study of neonates with cardiac disease admitted to the cardiac intensive care unit at our center during the 4-year period from January 1995 to December 1998. METHODS: Cardiac diagnosis and age at admission were analyzed for association with NEC among the 643-patient inception cohort. Demographic, preoperative, and operative variables were recorded retrospectively in 21 neonates with congenital heart disease who developed NEC and 70 control neonates matched by diagnosis and age at admission. Using parametric and nonparametric analysis, cases and controls were compared with respect to previously identified risk factors for NEC. RESULTS: Among the entire cohort of 643 neonates with heart disease admitted to the cardiac intensive care unit, diagnoses of hypoplastic left heart syndrome (odds ratio [OR] = 3.8 [1.6-9.1]) and truncus arteriosus or aortopulmonary window (OR = 6.3 [1.7-23.6]) were independently associated with development of NEC by multivariable analysis. In the case-control analysis, earlier gestational age at birth (36.7 +/- 2. 7 weeks vs 38.1 +/- 2.3 weeks), prematurity (OR = 3.9 [1.2-12.5]), highest dose of prostaglandin >0.05 microg/kg/minute (OR = 3.9 [1. 2-12.5]), and episodes of low cardiac output (meeting specific laboratory criteria) or clinical shock (OR = 6.5 [1.8-23.5]) correlated with the development of NEC. Earlier gestational age and episodes of low output were the only factors that remained significantly associated with NEC by multivariable analysis. Although there was no difference in hospital mortality between patients with and without NEC, mean hospital stay was significantly longer in those who developed NEC (36 +/- 22 days vs 19 +/- 14 days). CONCLUSIONS: The risk of NEC in neonates with congenital heart disease is substantial. Factors associated with an elevated risk of NEC in infants with heart disease include premature birth, hypoplastic left heart syndrome, truncus arteriosus, and episodes of poor systemic perfusion or shock. Heightened suspicion is warranted in newborns with these risk factors.
Asunto(s)
Enterocolitis Necrotizante/diagnóstico , Cardiopatías Congénitas/diagnóstico , Estudios de Casos y Controles , Causalidad , Estudios de Cohortes , Comorbilidad , Enterocolitis Necrotizante/tratamiento farmacológico , Enterocolitis Necrotizante/epidemiología , Femenino , Edad Gestacional , Cardiopatías Congénitas/epidemiología , Cardiopatías Congénitas/cirugía , Hospitalización , Humanos , Recién Nacido , Enfermedades del Prematuro/diagnóstico , Enfermedades del Prematuro/epidemiología , Unidades de Cuidado Intensivo Neonatal , Tiempo de Internación , Masculino , Análisis Multivariante , Evaluación de Resultado en la Atención de Salud , Prostaglandinas E/administración & dosificación , Prostaglandinas E/uso terapéutico , Factores de RiesgoRESUMEN
Male sexual dysfunction is a prevalent condition in the population, is a major health problem and has previously been both under diagnosed and under treated. There are now a number of treatments available that are safe and easy to use which provide an effective solution for most presenting patients. Oral drugs have recently become the first-line option for many men with about 60-70% of new presentations achieving success. Those who fail a trial of oral treatments have a number of other options available, which are able to provide erections sufficient for intercourse in many of the oral drug failures. All these options, their indications, side-effects and complications are outlined in this chapter.
Asunto(s)
Disfunción Eréctil/terapia , Antagonistas Adrenérgicos alfa/uso terapéutico , Adulto , Clomipramina/uso terapéutico , Eyaculación/efectos de los fármacos , Disfunción Eréctil/tratamiento farmacológico , Disfunción Eréctil/cirugía , Terapia de Reemplazo de Hormonas , Humanos , Masculino , Persona de Mediana Edad , Implantación de Pene , Fentolamina/uso terapéutico , Inhibidores de Fosfodiesterasa/uso terapéutico , Piperazinas/uso terapéutico , Prostaglandinas E/uso terapéutico , Psicoterapia , Purinas , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Citrato de Sildenafil , Sulfonas , Testosterona/uso terapéuticoRESUMEN
Es indispensable conservar la función renal de los pacientes con cirrosis hepática, ya que la insuficiencia renal se asocia con una alta morbimortalidad en dichos países. La vasoconstricción sistémica, la disminución del flujo sanguíneo renal y la disminución de metabolitos urinarios de prostaglandinas son importantes en la patogénesis de esta nefropatía. El misoprostol, prostaglandina sintética, puede modificar favorablemente algunos de los cambios en la hemodinamia renal de la cirrosis. Objetivo: Evaluar los cambios de la función renal en el paciente cirrótico con el uso de misoprostol. Metodología: se estudiaron 15 pacientes con cirrosis hepática que había desarrollado ascitis, con creatinina sérica menor a 1.5 mg/dL. Se determinaron: depuración de creatinina, volumen urinario, excreción de sodio urinario y la fracción excretada del mismo en 24 h., el filtrado glomerular y el flujo sanguíneo renal bilateral antes y después de la administración vía oral e misoprostol. Se aceptó un valor significativo a p < 0.05. resultados: Se encontró mejoría significativa únicamante en el flujo sanguíneo renal (p= 0.02), después de la administración de misoprostol. Sin embargo, al separar a los pacientes en dos grupos: los que usan diuréticos y aquellos que no los usan, se obtiene una diferencia significativa en el filtrado glomerular (p < 0.001), el flujo sanguíneo renal (p < 0.01) y la diurésis (p < 0.001). No hubo diferencias significativas en otros parámetros. Conclusiones: El uso de misoprostol en los pacientes cirróticos que utilizan diuréticos para el tratamiento de asitis y retención hídrica, mejora los parámetros de la función renal, al incrementar el flujo sanguíneo renal, el filtrado glomerular y la diuresis, actuando como vasodilatador en las arterias renales