The effects of vardenafil and pentoxifylline administration in an animal model of ischemic colitis

OBJECTIVES: Vardenafil enhances dilatation of vascular smooth muscle and inhibits platelet aggregation. The purpose of this study was to evaluate the clinical effects of vardenafil and pentoxifylline administration in an experimental model of ischemic colitis. METHODS: Forty female Wistar albino rats weighing 250-300 g were randomized into five experimental groups (each with n = 8) as follows:1) a sham group subjected to a sham surgical procedure and administered only tap water; 2) a control group subjected to a standardized surgical procedure to induce ischemic colitis and administered only tap water; 3) and 4) treatment groups subjected to surgical induction of ischemic colitis followed by the postoperative administration of 5 mg/kg or 10 mg/kg vardenafil, respectively; and 5) a treatment group subjected to surgical induction of ischemic colitis followed by postoperative administration of pentoxifylline at 50 mg/kg/day per day as a single dose for a 3-day period. All animals were sacrificed at 72 h post-surgery and subjected to relaparotomy. We scored the macroscopically visible damage, measured the ischemic area and scored histopathology to determine the severity of ischemia. Tissue malondialdehyde levels were also quantified. RESULTS: The mean Gomella ischemic areas were 63.3 mm2 in the control group; 3.4 and 9.6 mm2 in the vardenafil 5 and vardenafil 10 groups, respectively; and 3.4 mm2 in the pentoxifylline group (p = 0.0001). The mean malondialdehyde values were 63.7 nmol/g in the control group; 25.3 and 25.6 nmol/g in the vardenafil 5 and vardenafil 10 groups, respectively; and 22.8 nmol/g in the pentoxifylline group (p = 0.0001). CONCLUSION: Our findings indicate that vardenafil and pentoxifylline are effective treatment options in an animal model of ischemic colitis. The positive clinical effects produced by these drugs are likely due to their influence on the hemodynamics associated ...

Does sildenafil enhance the effect of tamsulosin in relieving acute urinary retention?

Objective To compare the safety and efficacy of combined therapy using sildenafil and tamsulosin for management of acute urinary retention (AUR) with tamsulosin alone in patients with benign prostate hyperplasia (BPH). Materials and Methods 101 patients were enrolled in a randomized placebo-controlled study from June 2009 to April 2012. Patients presenting with an initial episode of spontaneous AUR underwent urethral catheterization and then prospectively randomized to receive tamsulosin 0.4mg plus sildenafil 50mg in group A and tamsulosin 0.4mg plus placebo in group B for three days. Urethral catheter was removed three days after medical treatment and patient’s ability to void assessed at the day after catheter removal and seven days later. Patients who voided successfully were followed at least for three months. Results Mean age of patients was 59.64 ± 3.84 years in group A and 60.56 ± 4.12 years in group B (p value = 0.92). Mean prostate volume and mean residual urine were comparable between both groups (p value = 0.74 and 0.42, respectively). Fifteen patients in group A (success rate: 70%) and nineteen patients in group B (success rate: 62.7%) had failed trial without catheter (TWOC) at 7th day following AUR (p value = 0.3). No significant difference was noted between both groups regarding the rate of repeated AUR at one month and three month follow-up period (p = 0.07 and p = 0.45, respectively). Conclusion It seems that combination therapy by using 5-phosphodiesterase inhibitor and tamsulosin has no significant advantages to improve urinary retention versus tamsulosin alone. .

Phase 1 dose escalation study of rigosertib by 2-, 4-, or 8-hour infusion twice-weekly in patients with advanced cancer.

CONTEXT: Rigosertib, a potent, multi-kinase inhibitor that selectively induces mitotic arrest and apoptosis in cancer cells and is non-toxic to normal cells, is being developed for the treatment of solid tumors and hematological malignancies. AIMS: To determine the safety, doselimiting toxicities, and clinical activity of rigosertib administered by 2-, 4-, or 8-hour continuous IV infusion twice-a-week for 3 weeks out of a 4-week cycle in patients with advanced solid tumor or hematological malignancies; and to confirm the safety and tolerability of the recommended phase 2 dose (RPTD). SETTINGS AND DESIGN: Phase 1, open-label, dose-escalation study in men and women ≥18 years of age. MATERIALS AND METHODS: An escalation phase optimized the duration of infusion (2, 4, or 8 hours) of 3200 mg rigosertib twice-a-week for 3 weeks of a 4-week cycle; an expansion phase confirmed the maximum tolerated dose (MTD). STATISTICAL ANALYSIS USED: All data summaries were descriptive. PK parameters were estimated using compartmental analysis. RESULTS: 25 patients (16 male, 9 female, 26- 66 years, all Asian) were treated with rigosertib, 16 in the escalation phase; 9 in the expansion phase. MTD was determined to be 3200 mg as a 4-hour infusion and 2400 mg over 4 hours was declared to be the RPTD. Best response was stable disease in 5 of 14 evaluable patients, with a mean (range) of 90 (43-108) days. CONCLUSIONS: 2400 mg rigosertib as a 4-hour infusion was identified as the RPTD. Five patients achieved stable disease lasting 6-16 weeks.

Serum homocysteine levels and sildenafil 50 mg response in young-adult male patients without vascular risk factors.

The aim of the present study was to investigate serum homocysteine levels in patients with erectile dysfunction and to evaluate the relationship between serum homocysteine levels and response to the standard 50 mg phosphodiesterase 5 inhibitor treatment. Twenty-eight erectile dysfunction patients having normal vascular parameter according to Penile Doppler Ultrasonography and twenty healthy subjects were enrolled in the study. All subjects filled The International Index of Erectile Function (IIEF) questionnaire. A total of 4-6 doses of phosphodiesterase 5 inhibitor (sildenafil 50 mg) were given to patients. Later, they were divided into two groups as sildenafil responder and non-responder. Serum homocysteine levels were compared in groups based on sildenafil response. Compared with healthy subject, higher homocysteine levels were observed in patients with erectile dysfunction (p = 0.005), especially in sildenafil non-responder group (p = 0.005). There was significant negative correlation between homocysteine and IIEF scores in group responder to sildenafil treatment (r = -0.698, p = 0.008). Mean IIEF scores of patients with non-responder to sildenafil 50 mg were lower than those of controls (p = 0.0001), but mean IIEF scores of patients with responders approached values observed in control subjects (p = 0.002). The results indicated that measurement of serum homocysteine levels could be used as a marker for the evaluation of efficacy of phosphodiesterase 5 inhibitor and the selection of efficacious alternative therapies.

Effect of acute administration of sildenafil to rats with detrusor overactivity induced by chronic deficiency of nitric oxide

Purpose Recently, the effect of phosphodiesterase inhibitors (PDE5i) in the lower urinary tract symptoms (LUTS) associated to benign prostatic hyperplasia have been studied thoroughly. However, it remains unclear how the PDE5i improve LUTS. Therefore, the aim of the present study was to evaluate the potential of acute administration of the PDE5i sildenafil to improve detrusor overactivity (DO) induced by Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME), an nitric oxide sinthase (NOS) inhibitor, in rats. Materials and Methods Twenty-seven MALE adult Wistar Rats were divided into the following groups: (1) control, (2) L-NAME, (3) sildenafil alone, and (4) L-NAME + sildenafil. The NOS blocker L-NAME (20 mg/rat/day) was given in the drinking water. Sildenafil (100µg/kg) was administrated intravenously (i.v.) acutely, diluted in cremophor, propylene glycol and water. All animals underwent to anesthetized cystometograms. Results The chronic and systemic administration of L-NAME markedly increased the number of non voiding contractions (2.62 (± 0.89)), and frequency of micturition (1.97 (± 0.78)), as well increased volume threshold (2.83 mL (± 1.64)) compared with control group, the number of non voiding contractions (1.17 (± 0.75)), frequency of micturition (1.08 (± 0.65)) and volume threshold (1.16 mL (± 0.38)), p < 0.001, p = 0.01, and p = 0.04, respectively. Sildenafil infusion decreased the number of micturition cycles significantly from the baseline to end point (-0.93 (± 0.34)) in nitric oxide (NO) deficient animals compared with sildenafil infusion alone (control) in animals with normal NO level (0.13 (± 0.25)), p = 0.03. Conclusion Systemic reduction of nitric oxide causes detrusor overactivity and acute infusion of sildenafil reduces the number of micturition cycles in chronic NO-deficient rats. .

Sildenafil prevents the increase of extravascular lung water and pulmonary hypertension after meconium aspiration in newborn piglets

Meconium aspiration syndrome causes respiratory failure after birth and in vivo monitoring of pulmonary edema is difficult. The objective of the present study was to assess hemodynamic changes and edema measured by transcardiopulmonary thermodilution in low weight newborn piglets. Additionally, the effect of early administration of sildenafil (2 mg/kg vo, 30 min after meconium aspiration) on this critical parameter was determined in the meconium aspiration syndrome model. Thirty-eight mechanically ventilated anesthetized male piglets (Sus scrofa domestica) aged 12 to 72 h (1660 ± 192 g) received diluted fresh human meconium in the airway in order to evoke pulmonary hypertension (PHT). Extravascular lung water was measured in vivo with a PiCCO monitor and ex vivo by the gravimetric method, resulting in an overestimate of 3.5 ± 2.3 mL compared to the first measurement. A significant PHT of 15 Torr above basal pressure was observed, similar to that of severely affected humans, leading to an increase in ventilatory support. The vascular permeability index increased 57 percent, suggesting altered alveolocapillary membrane permeability. Histology revealed tissue vessel congestion and nonspecific chemical pneumonitis. A group of animals received sildenafil, which prevented the development of PHT and lung edema, as evaluated by in vivo monitoring. In summary, the transcardiopulmonary thermodilution method is a reliable tool for monitoring critical newborn changes, offering the opportunity to experimentally explore putative therapeutics in vivo. Sildenafil could be employed to prevent PHT and edema if used in the first stages of development of the disease.

Hipertensão arterial pulmonar hereditária apresentando-se como venopatia oclusiva / Occlusive venopathy phenotype in hereditary pulmonary arterial hypertension / Hipertensión arterial pulmonar hereditaria presentándose como venopatía oclusiva

Um homem de 33 anos com hipertensão arterial pulmonar hereditária teve um diagnóstico confirmado de venopatia oclusiva e microvasculopatia. O paciente permaneceu estável por 3 anos e meio recebendo sildenafila via oral, 75 mg 3x/dia (teste de caminhada de seis minutos de 375 m vs 105 m basal), mas necessitou da adição de bosentana (125 mg 2x/dia) posteriormente. A despeito do desfecho fatal após 5 anos, as observações sugerem um utilidade potencial dos vasodilatadores como uma ponte para o transplante de pulmão em casos selecionados com envolvimento venocapilar significante. A ocorrência de lesões veno-oclusivas e capilares na forma familiar da hipertensão arterial pulmonar enfatiza as dificuldades com a atual classificação da doença.

A 33-year-old male with severe hereditary pulmonary arterial hypertension had a confirmed diagnosis of occlusive venopathy and microvasculopathy. He remained stable for three and a half years on oral sildenafil, 75 mg t.i.d. (six-minute walked distance of 375 m vs 105 m at baseline), but required addition of bosentan (125 mg b.i.d.), subsequently. Despite the fatal outcome at five years post-diagnosis, the observations suggest a potential usefulness of vasodilators as a bridge for lung transplant in selected cases with significant venous/capillary involvement. The occurrence of veno-occlusive and capillary lesions in the familial form of pulmonary arterial hypertension reinforces the difficulties with the current classification of the disease.

Un hombre de 33 años con hipertensión arterial pulmonar hereditaria tuvo un diagnóstico confirmado de venopatía oclusiva y microvasculopatía. El paciente permaneció estable 3,5 años recibiendo sildenafila vía oral, 75mg 3x/ día (test de caminata de seis minutos de 375m vs. 105m basal), pero necesitó adición de bosentánana (125mg 2x/día) posteriormente. A despecho del desenlace fatal después de 5 años, las observaciones sugieren una utilidad potencial de los vasodilatadores como un puente para el transplante de pulmón en casos seleccionados con compromiso venocapilar significativo. La ocurrencia de lesiones veno-oclusivas y capilares en la forma familiar de la hipertensión arterial pulmonar enfatiza las dificultades con la actual clasificación de la enfermedad.

Protective effect of sildenafil citrate on contralateral testis injury after unilateral testicular torsion/detorsion

OBJECTIVES: This study was designed to investigate prevention of contralateral testicular injury with sildenafil citrate after unilateral testicular torsion/detorsion. METHODS: Thirty-seven adult male rats were divided into four groups: sham operated (group 1, n = 7), torsion/detorsion + saline (group 2, n = 10), torsion/detorsion + 0.7 mg of sildenafil citrate (group 3, n = 10) and torsion/detorsion + 1.4 mg of sildenafil citrate (group 4, n = 10). Unilateral testicular torsion was created by rotating the right testis 720º in a clockwise direction for 2 h in other groups, except for group 1, which was served as sham group. After torsion (2 h) and detorsion (2 h) periods, rats were killed. RESULTS: The level of reduced glutathion (GSH) (p<0.05) and the activities of catalase (p<0.01) and glutathione peroxidase (p<0.05) in the contralateral testis from group 2 were significantly lower and nitric oxide (NO) (p<0.05) level in the contralateral testis were significantly higher than those of group 1. Administration of low-dose sildenafil citrate (group 3) prevented the increases in malondialdehyde and NO levels and decreases in glutathione peroxidase activities and GSH values induced by testicular torsion. However, administration of high-dose sildenafil citrate (group 4) had no effect on these testicular parameters (p>0.05). Histopathological changes were detected in groups 2, 3 and 4. CONCLUSION: These results suggest that biochemically and histologically torsion/detorsion injury occurs in the contralateral testis following 2-h torsion and 2-h detorsion and that administration of low-dose sildenafil citrate before detorsion prevents ischemia/reperfusion cellular damage in testicular tissue.

Role of cGMP and cAMP in the hemodynamic response to intrathecal sildenafil administration

INTRODUCTION: Results from our laboratory have demonstrated that intracerebroventricular administration of sildenafil to conscious rats promoted a noticeable increase in both lumbar sympathetic activity and heart rate, with no change in the mean arterial pressure. The intracerebroventricular administration of sildenafil may have produced the hemodynamic effects by activating sympathetic preganglionic neurons in the supraspinal regions and spinal cord. It is well documented that sildenafil increases intracellular cGMP levels by inhibiting phosphodiesterase type 5 and increases cAMP levels by inhibiting other phosphodiesterases. OBJECTIVE: To examine and compare, in conscious rats, the hemodynamic response following the intrathecal administration of sildenafil, 8-bromo-cGMP (an analog of cGMP), forskolin (an activator of adenylate cyclase), or dibutyryl-cAMP (an analog of cAMP) in order to elucidate the possible role of the sympathetic preganglionic neurons in the observed hemodynamic response. RESULTS: The hemodynamic responses observed following intrathecal administration of the studied drugs demonstrated the following: 1) sildenafil increased the mean arterial pressure and heart rate in a dose-dependent manner, 2) increasing doses of 8-bromo-cGMP did not alter the mean arterial pressure and heart rate, 3) forskolin did not affect the mean arterial pressure but did increase the heart rate and 4) dibutyryl-cAMP increased the mean arterial pressure and heart rate, similar to the effect observed following the intrathecal injection of the highest dose of sildenafil. CONCLUSION: Overall, the findings of the current study suggest that the cardiovascular response following the intrathecal administration of sildenafil to conscious rats involves the inhibition of phosphodiesterases other than phosphodiesterase type 5 that increase the cAMP level and the activation of sympathetic preganglionic neurons.

Cardiovascular and hematologic effects produced by chronic treatment with etoricoxib in normotensive rats / Efeitos cardiovasculares e hematológicos produzidos pelo tratamento crônico com etoricoxib em ratos normotensos

PURPOSE: Evaluate the cardiovascular and hematological effects produced by chronic treatment with two dosis of etoricoxib in Wistar normotensive rats. METHODS: Thirty rats have been used and divided into one control group and two etoricoxib (10mg/kg and 30mg/kg) treatments groups for 60 days. The mean arterial pressure (MAP) was taken during the whole experimental period and at the end of this period, under anesthesia blood samples were taken, and further the withdrawn of the aorta, heart, brain, liver, and kidneys for the anatomopathologic study. RESULTS: The treatment with etoricoxib (30mg/Kg) produced a significant increase of the MAP from the 28th day of the experiment and from the platelets when compared to the control group and to the group treated with 10mg/Kg, besides producing a highly significant difference in hematocrit and in the red blood cells in relation to the control group. On the other hand the treatment with etoricoxib has not caused histopathological changes when compared to the control. CONCLUSION: These data show that the chronic treatment with etoricoxib leads to increase of the MAP, and to important hematological changes which seem to be associated to the hemoconcentration although not producing anatomopathological significant changes.

OBJETIVO: Avaliar os efeitos cardiovasculares e hematológicos produzidos pelo tratamento crônico com duas doses de etoricoxib em ratos Wistar normotensos. MÉTODOS: Foram utilizados 30 ratos divididos em um grupo controle e dois grupos tratamentos (10mg/kg e 30mg/kg) de etoricoxib por 60 dias. A pressão arterial média (PAM) dos animais foi aferida durante todo o período experimental e, ao final deste, sob anestesia, foram coletadas amostras de sangue, além da retirada da aorta, coração, cérebro, fígado e rins para estudo anatomopatológico. RESULTADOS: O tratamento com etoricoxib (30mg/Kg) produziu aumento significativo da PAM a partir do 28° dia do experimento e das plaquetas quando comparado ao grupo controle e ao grupo tratado com etoricoxib 10 mg/Kg, além de produzir diferença altamente significativa no hematócrito e nas hemácias em relação ao grupo controle. Por outro lado, o tratamento com etoricoxib, não produziu alterações histopatológicas quando comparado ao controle. CONCLUSÃO: Estes dados indicam que o tratamento crônico com etoricoxib produz aumento da PAM, além de importantes alterações hematológicas que parecem estar associadas à hemoconcentração, porém sem produzir alterações anatomopatológicas significativas.

Impacto do sildenafil sublingual na hipertensão pulmonar de pacientes com insuficiência cardíaca / Impacto del sildenafil sublingual en la hipertensión pulmonar de pacientes con insuficiencia cardiaca / Impact of sublingual sildenafil on pulmonary hypertension in patients with heart failure

FUNDAMENTO: A hipertensão pulmonar (HP) é fator de mau prognóstico no pós-operatório de transplante cardíaco (TC) e, desta forma, o estudo do grau de reversibilidade a vasodilatadores é obrigatório durante avaliação pré-operatória. OBJETIVO: Avaliar os efeitos hemodinâmicos pulmonares e sistêmicos do sildenafil como droga vasodilatadora durante o teste de reversibilidade da HP em candidatos a transplante cardíaco. MÉTODOS: Pacientes em fila para TC foram submetidos à medida de variáveis hemodinâmicas sistêmicas e pulmonares antes e após a administração de 100mg dose única e sublingual de sildenafil, durante cateterização cardíaca direita. RESULTADOS: Quatorze pacientes (idade: 47±12 anos, 71,4 por cento homens) com insuficiência cardíaca avançada, Fração de Ejeção (FE) 25 ± 7 por cento, Classe Funcional (CF- NYHA) CF III - 6 e CF IV - 8, foram avaliados neste estudo. A administração aguda de sildenafil mostrou ser eficaz na redução das pressões sistólica (62,4 ± 12,1 vs. 51,5 ± 9,6 mmHg, IC=95 por cento, p<0,05) e média (40,7 ± 7,3 vs. 33,8 ± 7,6 mmHg, IC=95 por cento, p <0,05) da artéria pulmonar. Houve também uma redução significativa da resistência vascular pulmonar (4,2 ± 3 vs. 2,0 ± 0,9 uWood, IC=95 por cento, p<0,05) e sistêmica (22,9 ± 6,8 vs. 18,6 ± 4,1 Wood, IC=95 por cento, p<0,05), associada a uma elevação do débito cardíaco (3,28 ± 0,79 vs. 4,12 ±1,12 uWood, IC=95 por cento, p<0,05) sem, no entanto, interferir de maneira significativa na pressão arterial sistêmica (87,8 ± 8,2 vs. 83,6 ± 9,1 mmHg, IC=95 por cento, p=0,3). CONCLUSÃO: O sildenafil sublingual é uma alternativa eficaz e segura como droga vasodilatadora durante o teste de reversibilidade da HP em portadores de insuficiência cardíaca e em fila para transplante cardíaco.

BACKGROUND: Pulmonary hypertension (PH) is a factor of poor prognosis in the postoperative period of heart transplant (HT) and thus, the study of the degree of reversibility to vasodilators is mandatory during the preoperative assessment. OBJECTIVE: To evaluate the pulmonary and systemic hemodynamic effects of sildenafil as a vasodilator during the PH reversibility test in patients that are candidates to HT. METHODS: Patients awaiting HT were submitted to the measurement of systemic and pulmonary hemodynamic variables before and after the administration of a single sublingual dose of 100 mg of sildenafil during right heart catheterization. RESULTS: Fourteen patients (age: 47±12 years, 71.4 percent men) with advanced heart failure Ejection Fraction (EF) 25 ± 7 percent, Functional Class (FC - NYHA) FC III - 6 and FC IV - 8, were evaluated in this study. The acute administration of sildenafil showed to be effective in decreasing the systolic (62.4 ± 12.1 vs 51.5 ± 9.6 mmHg, CI=95 percent, p<0.05) and mean (40.7 ± 7.3 vs 33.8 ± 7.6 mmHg, CI=95 percent, p <0.05) pressures of the pulmonary artery. There was also a significant decrease in the pulmonary (4.2 ± 3 vs 2.0 ± 0.9 uWood, CI=95 percent, p<0.05) and systemic vascular resistance (22.9 ± 6.8 vs 18.6 ± 4.1 Wood, CI=95 percent, p<0.05), associated to an increase in the cardiac output (3.28 ± 0.79 vs 4.12 ±1.12 uWood, CI=95 percent, p<0.05) without, however, significantly interfering in the systemic arterial pressure (87.8 ± 8.2 vs 83.6 ± 9.1 mmHg, CI=95 percent, p=0.3). CONCLUSION:The sublingual administration of sildenafil is an effective and safe alternative as a vasodilator during the PH reversibility test in patients with heart failure and awaiting a HT.

FUNDAMENTO: La hipertensión pulmonar (HP) se muestra factor de mal pronóstico en el postoperatorio de transplante cardiaco (TC) y, de esta forma, el estudio del grado de reversibilidad a vasodilatadores se vuelve obligatorio durante evaluación preoperatoria. OBJETIVO: Evaluar los efectos hemodinámicos pulmonares y sistémicos del Sildenafil como droga vasodilatadora durante la prueba de reversibilidad de la HP en candidatos a transplante cardiaco. MÉTODOS: Pacientes en fila para TC fueron sometidos a la medición de variables hemodinámicas sistémicas y pulmonares, antes y luego de la administración de 100mg en dosificación única y sublingual de Sildenafil, durante cateterización cardiaca derecha. RESULTADOS: Se evaluaron en este estudio a 14 pacientes (edad: 47±12 años, el 71,4 por ciento varones) con insuficiencia cardiaca avanzada, fracción de eyección (FE) 25 ± 7 por ciento, clase funcional (CF-NYHA) CF III - 6 y CF IV - 8. La administración aguda de Sildenafil se mostró eficaz en la reducción de las presiones sistólica (62,4 ± 12,1 vs 51,5 ± 9,6 mmHg, IC=95 por ciento, p<0,05) y media (40,7 ± 7,3 vs 33,8 ± 7,6 mmHg, IC=95 por ciento, p <0,05) de la arteria pulmonar. Hubo también una reducción significativa de la resistencia vascular pulmonar (4,2 ± 3 vs 2,0 ± 0,9 uWood, IC=95 por ciento, p<0,05) y sistémica (22,9 ± 6,8 vs 18,6 ± 4,1 Wood, IC=95 por ciento, p<0,05), asociada a una elevación del débito cardiaco (3,28 ± 0,79 vs 4,12 ±1,12 uWood, IC=95 por ciento, p<0,05) sin, con todo, interferir de manera significativa en la presión arterial sistémica (87,8 ± 8,2 vs 83,6 ± 9,1 mmHg, IC=95 por ciento, p=0,3). CONCLUSIÓN: El Sildenafil sublingual resulta una alternativa eficaz y segura como droga vasodilatadora durante la prueba de reversibilidad de la HP en portadores de insuficiencia cardiaca y en fila para transplante cardiaco.

Efficacy of etoricoxib for pain relief during endometrial biopsy; a double blind randomized controlled trial.

OBJECTIVE: To compare the efficacy of oral etoricoxib and placebo for pain relief during endometrial biopsy. MATERIAL AND METHOD: A double-blind, randomized controlled trial that included 80 women who underwent endometrial biopsy was done at Thammasat University Hospital between 1 September 2005 and 30 June 2006. Forty women were randomly allocated to the etoricoxib group (120 mg, tablet) and 40 to the placebo group. The main outcome was the patient's assessment of intensity of pain measured by visual analog scale (VAS) before speculum insertion, during endometrial biopsy, immediately after endometrial biopsy, and 30 minutes after endometrial biopsy. Satisfactory score was also evaluated. RESULTS: Demographic data including age, BMI, previous vaginal deliveries, previous pelvic surgery and history of curettage were not significantly different between the etoricoxib group and the placebo group. Mean pain score in the etoricoxib group was not significantly lower when compared with the placebo group during endometrial biopsy (5.0 +/- 1.7 versus 5.25 +/- 2.2, p = 0.7) and immediately after endometrial biopsy (2.1 +/- 2.2 versus 2.8 +/- 1.7, p = 0.1) but significantly lower at 30 minutes after endometrial biopsy (0.2 +/- 0.5 versus 0.6 +/- 0.8, p = 0.01). Mean satisfactory score was significantly higher in the etoricoxib group (6.9 +/- 1.8 versus 5.1 +/- 2.3, p = 0.001). CONCLUSION: A single oral dose of etoricoxib for reduction of pain during endometrial biopsy had not significantly lower the pain score during the procedure compared with the placebo. However mean satisfactory score in the etoricoxib group was higher with statistically significant difference. Also the authors found no serious adverse effects of this drug.

Prevention of post operative pain after abdominal hysterectomy by single dose etoricoxib.

OBJECTIVE: To test whether a reduction in post operative morphine consumption could be achieved by a single-dose of etoricoxib before induction of anesthesia. DESIGN: Randomized, double-blind, placebo-controlled study. MATERIAL AND METHOD: Two hours before surgery, patients undergoing transabdominal hysterectomy (under general anesthesia) were randomized to a single oral dose of 1) etoricoxib 120 mg (n = 17), 2) etoricoxib 180 mg (n = 17), or 3) placebo (n = 15). Intravenous morphine was given for patient-controlled analgesia (PCA) device. Morphine consumption, pain scores both at rest and on coughing, and side-effects were recorded at 1, 2, 4, 8 and 24 h after surgery. Patients' global evaluation of study medication was assessed at the end of the present study. RESULTS: Etoricoxib provided greater clinical benefit than the placebo in terms of mean morphine in milligram at 24 hour consumption (stardard deviation): a) 26.4 mg (SD of 11.2) for etoricoxib 120 mg; b) 27.2 mg (SD of 9.9) for etoricoxib 180 mg; and, c) 36.6 mg (SD of 8.9) for the placebo group. At 8 h post surgery, pain both at rest and on coughing in the active drug groups was significantly less than in the placebo, while pain on coughing was significantly less at 24 h. Patients reported better global satisfaction and less somnolence in the etoricoxib groups. CONCLUSION: Single dose etoricoxib 180 mg given before surgery provides the same analgesic effect as 120 mg for post operative pain after an abdominal hysterectomy.

Additive Antinociception between Intrathecal Sildenafil and Morphine in the Rat Formalin Test

The possible characteristics of spinal interaction between sildenafil (phosphodiesterase 5 inhibitor) and morphine on formalin-induced nociception in rats was examined. Then the role of the opioid receptor in the effect of sildenafil was further investigated. Catheters were inserted into the intrathecal space of male Sprague-Dawley rats. For induction of pain, 50 microliter of 5% formalin solution was applied to the hindpaw. Isobolographic analysis was used for the evaluation of drug interaction between sildenafil and morphine. Furthermore, naloxone was intrathecally given to verify the involvement of the opioid receptor in the antinociception of sildenafil. Both sildenafil and morphine produced an antinociceptive effect during phase 1 and phase 2 in the formalin test. The isobolographic analysis revealed an additive interaction after intrathecal delivery of the sildenafil-morphine mixture in both phases. Intrathecal naloxone reversed the antinociception of sildenafil in both phases. These results suggest that sildenafil, morphine, and the mixture of the two drugs are effective against acute pain and facilitated pain state at the spinal level. Thus, the spinal combination of sildenafil with morphine may be useful in the management of the same state. Furthermore, the opioid receptor is contributable to the antinocieptive mechanism of sildenafil at the spinal level.

Sildenafil for pulmonary hypertension secondary to congenital heart diseases.

OBJECTIVE: The purpose of this study was to evaluate the effects of oral Sildenafil for treatment of pulmonary hypertension secondary to congenital heart diseases. METHODS & RESULTS: Twelve patients with un-repaired congenital heart diseases resulting in significant pulmonary hypertension were enrolled in a prospective trial of oral Sildenafil treatment for 12 weeks. The outcomes measured were change in the systemic oxygen saturations, 6-minute walk test distance, and New York Heart Association class. The systemic blood pressure and visual symptoms were monitored for evaluating the tolerability of Sildenafil. The mean age was 25.7+/-14.4 years. The mean pulmonary vascular resistance before treatment was 17.4 Wood units. After 12 weeks of sildenafil, an increase in oxygen saturations (87.8+/-5.3%-90.25+/-4%, p=0.04) with an associated increase of one New York Heart Association class (p=0.009) was noted. A non-statistically significant increase in the 6-minute walk test distance (310.33+/-42-333.75+/-54.6 meters, p=0.47) was also noted. Sildenafil was well-tolerated with no significant change in systemic blood pressure or visual side-effects. CONCLUSION: Oral Sildenafil is well-tolerated and produces some improvement in the oxygenation and functional status of patients with pulmonary hypertension secondary to congenital heart diseases.

Oral etoricoxib for pain relief during fractional curettage: a randomized controlled trial.

OBJECTIVE: To compare the efficacy of oral etoricoxib and placebo combined with paracervical block for pain relief during fractional curettage MATERIAL AND METHOD: A double-blind, randomized controlled trial that included 220 women who underwent fractional curettage and received paracervical block for pain relief was done at Ramathibodi Hospital between September 2005 and June 2006. One hundred and ten women were randomly allocated to the etoricoxib group (90 mg, tablet) and 110 to the placebo group. The main outcome was the patient's assessment of intensity of pain measured by verbal rating scales after speculum insertion, during fractional curettage, immediately after curettage, and 30 minutes after curettage. RESULTS: Demographic data including age, previous vaginal deliveries, and history of curettage were not significantly different between etoricoxib group and placebo group. Most common indication for fractional curettage was menometrorrhagia in both groups. Pain score in etoricoxib group was significant lower during fractional curettage (5 vs. 6, p = 0.04), immediately after curettage (2 vs. 3, p = 0. 009), and 30 minutes after curettage (0 vs. 1, p = 0.003). Comparing the number of patients with mild pain (score 0-3), there were significant higher number of mild pain patient at the time during curettage (39 vs. 20 cases), immediate after curettage (78 vs. 60 cases), and 30 minutes after curettage (107 vs. 100 cases) in etoricoxib group. CONCLUSION: Combination of etoricoxib with paracervical block for reduction of pain during fractional curettage had statistically significant lower pain scale when compared with placebo with paracervical block. However the difference was small and may have questionable clinical significance.

Sildenafil masticable, análisis prospectivo de nueva presentación farmacológica / Cheweable sildenafil: prospective analysis of a new presentation

La disfunción eréctil es una patología de alta frecuencia, especialmente en población masculina de mayor edad. La erección está dada fundamentalmente por la activación del sistema parasimpático, por acción del óxido nítrico y aumento de GMP cíclico; es así como fármacos como Sildenafil que disminuyen la eliminación de GMP cíclico al inhibir la actividad de la 5 fosfodiesterasa, potencian la mantención de dicha erección. Recientemente se lanzó al mercado la presentación masticable de este fármaco, lo que eliminaría el primer paso hepático de la presentación oral clásica. En este estudio, se analizaron 20 pacientes con disfunción eréctil sin comorbilidad asociada, los que consumieron la forma masticable; con el objetivo de evaluar eficacia clínica y efectos adversos. Los resultados obtenidos muestran que existe un alto grado de satisfacción de usuario en cuanto a forma de presentación, tiempo de administración y eficacia, y que los efectos adversos no difieren a los de la presentación tradicional. Se propone realizar estudios prospectivos comparativos de ambas presentaciones y otros inhibidores de la 5 fosfodiesterasa, para confirmar estos resultados preliminares.

Erectil dysfunction is a very frequent pathology in the elderly male. Erections are activated mainly by the parasympathic system, caused by nitric oxide and the increase of cyclic cGMP; it is because of this that drugs like Sildenafil improve partial erections by inhibiting the enzyme that facilitates the reduction of cyclic guanosine monophosphate (cGMP). Recently a chewable new form of this drug entered the market,it is deemed to avoid hepatic transformation of the drug. In this study we analyzed 20 patients witherectile dysfunction without other associated comorbidities that were treated with this drug. Results showed that patients were highly satisfied with the form of presentation, the dosage regimen, and efficacy. Side effects are no different from the other and more traditional version. We will conduct prospective comparative studies of both versions of the drugs and other inhibitors of the cGMP specific phosphodiesterase type 5,to confirm these preliminary results.

A Case of Complete Regression of Hepatocellular Carcinoma during Administration of COX-2 Inhibitor / 대한간학회지

Overexpression of cyclooxygenase-2 (COX-2) has been associated with hepatocarcinogenesis. Inhibitors of COX-2 have proapoptotic and antiproliferative effects on malignant tumors and inhibit tumor invasion to the surrounding tissues. We report here a case of complete regression of advanced hepatocellular carcinoma (HCC) during COX-2 inhibitor administration. An eighty-year-old female was diagnosed as an advanced HCC, which was associated with HCV infection. She received COX-2 inhibitor for 3 months due to degenerative arthritis of both knees. Tumor enhancement on arterial phase CT completely disappeared without specific treatment for the HCC, and the tumor size decreased on the follow-up CT scan.

Enfermedadf por igA lineal / Lineal igA disease

Presentamos dos pacientes con enfermedad por ig A lineal, de 2 y 3 años de edad respectivamente, ambos del sexo masculino, se llegó al diagnóstico por la clínica dermatológica, la histología y la inmunofluorescencia directa, donde se detectó ig A lineal en la zona de la membrana basal. Fueron tratados con diamino difenil sulfona (DAPS), con una rápida y efectiva respuesta y con antihistamínicos (difenhidramina) para mejorar el prurito. Los controles se realizaron periódicamente desde el comienzo de la afección hasta la actualidad. Consideramos que la enfermedad por igA lineal no es una dermatosis muy frecuente en la infancia, pero se debe tener presente. Loas diagnósticos diferenciales obligados so: la dermatitis herpetiforme y el penfigoide ampollar, sin dejar de tener en cuenta otras afecciones ampollares no geneticas como el impétigo ampollar, la epidermólisis ampollar adquirida de la infancia y el eritema poliformo ampollar